Nervous System Dysfunctions

Learning Outcomes and Foundation of Nervous System Disorders

  • General Scope of Behavior

    • Everything observed and categorized as behavior is an direct function of the nervous system.

    • The nervous system is subject to the largest number of disorders compared to any other system in the human body.

  • Impact of Disorders

    • Nervous system disorders affect cognitive function.

    • Disorders impact movement and physical senses (motor and sensory functions).

  • Multi-Disciplinary Research and Investigation

    • Numerous disciplines are involved in the investigation of the nervous system:

    • Neurologists

    • Neuroanatomists

    • Neurosurgeons

    • Psychologists

    • Educators

    • Social Scientists

  • Etiology (Causes) of Disorders

    • Multiple causes contribute to nervous system dysfunction:

    • Birth injury

    • Hypoxia (lack of oxygen)

    • Hypoglycemia (low blood sugar)

    • Jaundice

    • Trauma

    • Cancer

    • Disease

Consciousness: Manifestation of Brain Function

  • Definition of Consciousness

    • A state of awareness regarding the self and surroundings.

    • The ability to respond to stimuli.

    • Higher or cerebral hemisphere function.

  • Two Primary Components of Consciousness

    • Content of Thought: Involves thinking and moods.

    • Arousal: Being aware and able to respond to surroundings. This is a function of the reticular activating system (RAS).

  • Causal Categories for Alterations of Consciousness

    • Structural Defects: Characterized by asymmetrical signs and symptoms. These often result from cerebrovascular (CV) accidents, tumors, or trauma.

    • Metabolic Defects: Characterized by symmetrical signs and symptoms. These result from:

    • Electrolyte imbalance

    • Hypoglycemia

    • Decreased oxygen

    • Drugs and toxins

    • Diseases

    • Psychogenic Factors: The patient appears awake but is unresponsive.

Clinical Evaluation of Consciousness and Neurological Status

  • Levels of Consciousness (LOC)

    • Confusion: Slow and muddy mental function.

    • Disorientation: Lacking clarity regarding time and space.

    • Lethargy: The patient sits or lies there; appears drowsy.

    • Obtundation: Characterized by dulled indifference; the patient repeatedly falls asleep.

    • Stupor: A state of deep sleep from which the patient can only be awakened by vigorous stimuli.

    • Coma: No response to stimuli. Spinal cord and postural reflexes may still be elicited.

  • Pattern of Breathing

    • As consciousness decreases, breathing patterns change and typically become more profound.

  • Pupillary Response Assessment

    • Evaluations include pupil size, position, and response to light.

    • The Oculomotor nerve (Cranial Nerve III) controls pupil diameter and arises from the mesencephalon (midbrain).

  • Eye Movement and Cranial Nerves

    • Oculomotor Nerve (III): Controls three eyeball muscles; essential for determining the level of brain injury.

    • Trigeminal Nerve (V): Arises from the pons and controls blinking. An absent blink reflex indicates pons involvement.

    • Cortical Control: The cerebral cortex controls CN III, IV, and VI, which collectively allow eyeball movement.

  • Skeletal Muscle Responses

    • Reflexes: May present as hyperreflexia (increased), hyporeflexia (decreased), or areflexia (absent).

    • Movement Deficits:

    • Paresis: Weakness or partial loss of voluntary movement.

    • Paralysis: Total loss of motor function.

    • Hemiparalysis: Affects upper and lower limbs on one side of the body.

    • Paraplegia: Affects the lower extremities.

    • Quadraplegia: Affects both upper and lower extremities.

  • Muscle Size and Tone

    • Size: Atrophy (wasting) or hypertrophy (overgrowth).

    • Tone: Reflects nervous system activity.

    • Hypotonia: Decreased muscle tone.

    • Hypertonia: Increased muscle tone.

    • Spasticity: A gradual increase in tone followed by an abrupt decrease (clasp knife response).

    • Rigidity: Characterized by constant muscle contraction.

Coma Etiology and Determination of Brain Death

  • Incidence of Coma Causes

    • Metabolic/Toxic: Ingestion of drugs or chemicals.

    • Organ Failure: Liver or kidney failure leading to the buildup of toxic products.

    • Electrolyte Imbalances.

    • Hypoxic Metabolic: Caused by cardiac arrest, asphyxia, or ischemia (e.g., blood clot).

    • Traumatic: Primary hemorrhage or mass lesions.

  • Exclusion of Reversible Causes (Preconditions)

    • Before determining brain death, physicians must exclude:

    • Intoxication

    • Depressant drugs

    • Muscle relaxants

    • Primary hypothermia

    • Hypovolemic shock

    • Metabolic and endocrinal disturbances

  • Diagnosis of Brain Death (NCBI - NIH Criteria)

    • Essential Findings: Coma, absence of brainstem reflexes, and apnea.

    • Context: Should be considered in patients with massive, irreversible brain injury of an identifiable cause.

    • Legal Status: A patient determined to be brain dead is legally and clinically dead.

  • Uniform Determination of Death Act (UDDA)

    • Criteria for Cessation of Entire Brain Function: Physicians must determine unresponsive coma, absence of brainstem reflexes, and absence of respiratory drive following a CO2 challenge.

    • Ensuring Irreversibility: Determine cause of coma, exclude mimicking medical conditions, and observe the patient for a period of time.

    • Proposed Revisions: There is a call to revise the UDDA to match clinical practice via "Neurorespiratory Criteria." This focuses on the permanent loss of capacity for consciousness, spontaneous breathing, and brainstem reflexes. Some argue that the presence of functions like the absence of diabetes insipidus suggests lingering brain function not currently captured by legal text.

  • Observation and Evidence Levels

    • Level U (Data inadequate): Insufficient evidence for the minimally acceptable observation period or the utility of newer ancillary tests.

    • Level C (Low confidence): Weak evidence that complex-spontaneous motor movements and false-positive ventilator triggering may occur in brain-dead patients.

Acute Confusional State and Dementia

  • Acute Confusional State (ACS)

    • Definition: Purposeful response to some stimuli but patient is sleepy, disoriented, inattentive, or agitated.

    • Causes of ACS:

    • Metabolic: Drugs (Ethanol, sedatives, opioids, hallucinogens).

    • Withdrawal: Ethanol or sedatives.

    • Endocrine and electrolyte disorders.

    • Nutritional: Wernicke’s encephalopathy; Vitamin B12 deficiency.

    • Organ Failure: Hepatic encephalopathy; Reye’s syndrome (causes brain and liver swelling).

    • Other: Meningitis/encephalitis, vascular disorders, head trauma, seizures, and acute functional psychosis (schizophrenia, mania, stress reaction).

  • Dementia

    • Definition: Generalized impairment of cognitive function; consciousness is not depressed.

    • Signs: Decreased orientation, general knowledge, memory, and judgment.

    • Pseudodementia: Affects 14%14\% of suspected dementia patients; caused by depression, psychiatric disorders, amnesia, or ACS.

  • Alzheimer’s Disease (AD)

    • Scope: Accounts for 60%60\% of dementia cases in the U.S.; clinical duration is approximately 1010 years.

    • Brain Pathophysiology:

    • Decrease in Acetylcholine: Linked to reductions in choline acetyltransferase and acetylcholinesterase.

    • Neurofibrillary Tangles: Composed of tau protein.

    • Neuritic Plaques: Accumulation of beta-amyloid protein.

  • Tau Protein and Experimental Findings

    • Amyloid beta (A-beta) induces impairment of Long-Term Potentiation (LTP) in the hippocampus, which is a measure of memory.

    • Studies in knock-out mice (lacking tau) show that the absence of tau prevents A-beta induced impairment of LTP.

    • A-beta regulates the phosphorylation of tau; hyperphosphorylation leads to paired helical filaments and tangles, disrupting microtubule stability provided by tau and tubulin.

    • New finding: Alzheimer's pathology (specifically distorted tau protein) may spread like an infection from brain cell to brain cell.

  • Alzheimer's Etiology and Statistics

    • Etilogy unknown in 75%75\% of cases; factors include aging, trauma, viruses, and toxins.

    • Autosomal dominant form: 10%10\% of cases.

    • Genetic Link: Risk increases with first-degree relatives. People with Trisomy 21 often develop AD in their 4040s because Chromosome 21 codes for the beta-amyloid protein.

  • Pharmacological Treatments for Alzheimer's

    • Leqembi (2023 Approval): First amyloid-directed antibody; reduces plaques.

    • Donepezil: Most commonly prescribed; acetylcholinesterase inhibitor.

    • Saracatinib: Human trials underway as a production blocker to reduce beta-amyloid formation.

    • Other trials: Solanezumab (mild effect), Gantenerumab (no benefit), Aducanumab (slight benefit).

    • Risk Factors: Use of antidepressants, antiparkinson drugs, antipsychotics, antimuscarinics (for overactive bladder), and antiepileptics may increase dementia risk.

  • Alcholism and other Dementias

    • Multi-infarct dementia: Second most common cause.

    • Huntington’s disease: Autosomal dominant; early 4040s; progressive chorea and dementia.

    • Alcoholism: Causes clear brain shrinkage. Example: A 5757-year-old alcoholic with a lifetime consumption of 1866 kg1866\,kg (625 gallons625\,gallons) compared to a control subject consumption of 60 kg60\,kg (20 gallons20\,gallons).

Seizure Disorders

  • Definition: Sudden disorderly discharge of cerebral neurons altering brain function and consciousness.

  • Etiology:

    • Cerebral Lesions: Tumors, malformations, infections, vascular diseases.

    • Biochemical: Addiction/withdrawal, hypoglycemia, hypocalcemia.

    • Trauma: Injury, surgery.

    • Epilepsy: Chronic disorder with no underlying identifiable cause.

  • Electroencephalogram (EEG) Rhythms

    • Normal: Beta, Alpha, Theta, Delta.

    • Seizure EEG: Shows disorderly discharge patterns in parietal, occipital, frontal, or temporal lobes.

  • Seizure Induction and Types

    • Triggers: Blinking lights, fatigue, fever, infection, hypoglycemia, odors.

    • Type I (Partial): Local, unilateral; begins in cortex; "Jacksonian march" (moves distal to proximal).

    • Type II (Generalized): Multifocal; involves both brain sides.

    • Type III (Unclassified): Fits no other category.

    • Type IV (Status Epilepticus): Two or more consecutive seizures without recovery. A medical emergency due to brain hypoxia.

    • Absence (Petit Mal): Patient stops mid-sentence or mid-walk for a few seconds, then resumes.

Motor Dysfunction and Posturing

  • Abnormal Postures

    • Dystonia: Abnormal posture resulting from muscle contractions.

    • Parkinsonism: Stooped, bent posture.

    • Decerebrate Posture: Results from upper brain stem damage. Hyperextension and medial rotation of upper/lower extremities; wrists pronated; plantar flexion.

    • Decorticate Posture: Results from damage to corticospinal tracts. Upper extremities flexed at elbows/wrists (on chest); lower extremities extended and internally rotated; plantar flexion.

    • Akinesia: Loss of voluntary movement or facial expression (masked facies).

  • Abnormal Movements

    • Hyperkinesia: Excessive movement.

    • Fasciculations: Muscles "jump under the skin" due to rapid motor unit contraction.

    • Tremor: Rhythmic oscillating movement. Types: Tremor at rest (Parkinsonism) vs. Intention tremor (during purposeful movement).

    • Clonus: Sustained muscle contraction.

    • Dyskinesia: Category of involuntary movements.

    • Athetosis: Continuous, worm-like movements.

    • Chorea: Brief, graceful, dance-like movements of upper extremities.

    • Ballism: Violent flinging of extremities; usually unilateral.

  • Motor Pathway Anatomy

    • Pyramidal Tracts: Corticospinal (body) and Corticobulbar (head/neck) for voluntary movement.

    • First-Order (Upper) Neuron: Starts in the precentral gyrus of the cerebral cortex, decussates (crosses) in the medulla, descends the lateral column.

    • Second-Order (Lower) Neuron: Arises in the anterior (ventral) horn of the spinal cord, innervates skeletal muscle.

    • Extrapyramidal System: Basal ganglia, mesencephalon, and cerebellum.

Clinical Motor Syndromes

  • Upper Motor Neuron (UMN) Syndrome

    • Phase 1: Spinal Shock: Complete cessation of cord activity; areflexia, flaccid paralysis; lasts days/weeks.

    • Phase 2: Spastic paralysis, hyperreflexia, hypertonia, and Babinski’s sign.

  • Lower Motor Neuron (LMN) Syndrome

    • Signs: Flaccid paralysis, hyporeflexia, hypotonia, and atrophy.

    • Example: Polio.

  • Extrapyramidal Motor Syndrome

    • Involves basal ganglia, cerebellum, or mesencephalon.

    • Basal Ganglia Lesion Hallmark: Involuntary movements; rigidity; little to no paralysis; normal reflexes.

    • Cerebellum Syndrome Hallmark: Difficulty in co-ordination, equilibrium, and gait. Defect is ipsilateral (patient staggers toward lesion). Includes difficulty with rapidly alternating movements.

Unifocal Cortical Lesions and Communication Disorders

  • Agnosia: Inability to recognize form/function of objects despite intact senses.

    • Tactile (Asterognosis): Can't recognize object in a closed fist.

    • Spatial: Can't navigate familiar places.

    • Visual: Can't recognize faces, pictures, or objects.

  • Specific Deficits

    • Alexia: Inability to read.

    • Agraphia: Inability to write.

    • Acalculia: Inability to perform simple math.

    • Apraxia: Inability to carry out voluntary movement (not due to paralysis or sensory loss).

  • Dysphasia (Language Impairment)

    • Often caused by middle cerebral artery CVA affecting nutrition to specific brain areas.

    • Expressive Dysphasia (Broca's): Comprehension is intact; difficulty finding or producing words.

    • Receptive Dysphasia (Wernicke's): Temporal lobe lesion. Patient can hear but cannot make sense of words; uses nonsense words or abnormal rhythm.

    • Aphasia: Complete loss of speech production or comprehension.

Cerebral Homeostasis and Intracranial Pressure (ICP)

  • Causes of Increased ICP

    • Trauma, edema, bleeding, tumor, infection, excessive Cerebrospinal Fluid (CSF).

  • Clinical Signs of Increased ICP

    • Papilloedema: Bulging of the optic disc.

    • Bulging fontanelles in infants.

    • Alterations in LOC.

  • Stages of Compensation

    • Stage I: Vasoconstriction and shifting of CSF to reduce pressure.

    • Stage II: Arterial blood pressure rises to maintain cerebral perfusion.

    • Stage III: Decompensation; ICP equals arterial pressure; perfusion stops, neurons die from hypoxia/high CO2.

    • Stage IV: Herniation. Brain tissue shifts into adjacent compartments.

    • Supratentorial: Shifts between anterior, middle, or posterior fossae.

    • Infratentorial: Tissue shifts into the foramen magnum.

  • Arnold-Chiari Malformation: Obliteration of cisterna magna and displacement of cerebellum; causes non-communicating hydrocephalus, headaches, and swallowing difficulty.

Head and Spinal Cord Trauma

  • Cerebral Edema Types

    • Vasogenic: Most common; increased capillary permeability leads to protein/water leakage.

    • Metabolic: Toxins alter neuronal membrane permeability; sodium/water enter cells causing death.

  • Closed (Blunt) Head Trauma

    • Coup: Injury at impact site.

    • Contracoup: Injury opposite impact site.

    • Concussion: Transient; loss of consciousness for <5< 5 minutes.

    • Contusion: Bruising of tissue.

    • Laceration: Tearing of tissue.

  • Hematomas

    • Epidural: Above dura, under skull. Usually middle meningeal artery; temporal lobe is frequent site.

    • Subdural: Between dura and brain. Usually dural venous sinuses.

    • Acute: 50%50\% mortality; rapid development.

    • Subacute: Slower; better prognosis.

    • Chronic: Slowest; seen in elderly (atrophy) or those on anticoagulants.

    • Intracranial: Bleeding within brain tissue.

  • Open (Penetrating) Trauma: Fracture of skull; dura torn; high infection risk.

  • Spinal Cord Trauma

    • Common sites: C1C1, C2C2, C4C4-C6C6, T11T11-T12T12.

    • Risks: Phrenic nerve compromise (C3C3-C5C5) affects the diaphragm.

    • Spinal Shock: Transient period of absent cord activity.

Cerebrovascular and Disc Diseases

  • Low Back Pain

    • Degenerative Disc Disease: Narrowing and fibrosis due to aging.

    • Herniated (Slipped) Disc: Nucleus pulposus oozes into annulus fibrosis, compressing the cord. Often lumbosacral.

  • Cerebrovascular Accident (CVA/Stroke)

    • 3rd leading cause of death.

    • Types:

    • Thrombotic (53%−87%53\%-87\%): Associated with atherosclerosis and oral contraceptives.

    • Transient Ischemic Attack (TIA): Blockage resolves within 2424 hours; precedes major strokes.

    • Embolic (31%31\%): Moving mass.

    • Hemorrhagic (16%16\%): Bleeding into brain tissue.

    • FAST Assessment: Face Drooping, Arm Weakness, Speech Difficulty, Time to call 9-1-1.

    • Treatment window: Thrombolytics within 33 hours of first symptom.

  • Vascular Abnormalities

    • Aneurysm: Weakened arterial wall; often at Circle of Willis bifurcations; linked to Marfan’s syndrome.

    • Arteriovenous Malformation: Fistulae between arteries/veins; hallmark is a systolic bruit (murmur) in young people.

    • Subarachnoid Hemorrhage: Bleeding into subarachnoid space; clogs arachnoid villi, preventing CSF resorption.

Headaches, Infections, and Specific Diseases

  • Headaches (Cephalalgia)

    • Migraine: Chronic, unilateral, temporal/vascular. Triggers: red wine, nitrites (meats), tyramine (cheese), phenylephedrine (chocolate).

    • Cluster: Several episodes per day (<2< 2 hours); temporal/eye focus; favors males.

    • Muscle Tension: Cramp-like; felt like a tight band around the head.

  • CNS Infections

    • Meningitis: Signs include nuchal rigidity (stiff neck) and photophobia. Causative bacteria include Neisseria meningitides, Streptococcus pneumoniae, and Haemophilus influenzae.

    • Encephalitis: Viral inflammation (insect-borne, herpes simplex, or mumps).

  • Degenerative Motor Disorders

    • Parkinsonism: Degeneration of substantia nigra; dopamine deficiency. Signs: Pill-rolling tremor at rest, festinating gait (rapid small steps), masked facies.

    • Multiple Sclerosis (MS): Demyelination in CNS; affects white females (2020-4040 years) far from equator; associated with increased IgG levels. Hallmark: paralysis of medial rectus muscle.

    • Amyotrophic Lateral Sclerosis (ALS): Death of both upper and lower motor neurons; muscle weakness leads to paralysis.

    • Multiple Sclerosis Medications: Avonex, Betaseron, Copaxone, Extavia, Gilenya, Novantrone, Rebif, Tysabri.

Peripheral Nervous System (PNS) Disorders

  • Neuropathy: Affects cranial/spinal nerves; involves sensory and motor components. Sensation loss feels like a "glove or stocking."

  • Diabetic Neuropathy: Metabolic/vascular conditions damage vasa nervorum (small vessels), causing ischemia and nerve damage; increases risk of infection and gangrene.

  • Radiculopathy: Compression of spinal nerve roots following a dermatomal (sensory) or myotomal (motor) distribution. Example: Sciatica.