Neuropathology

Neurological Disorders

Paul Kelner, M.D.


• Overview and Organization of the Nervous System

• Central Nervous System – brain and spinal cord

• Peripheral nervous system – cranial nerves and spinal nerves

Divisions of the Nervous System

Neurological Disorders:Organization of the Nervous System

• The Central Nervous System• The Brain • The Spinal Cord• Motor pathways (in spinal cord) -

efferent• Sensory pathways (in spinal cord)

- afferent

Central Nervous System

Afferent and Efferent Pathways

Neurological Disorders:Organization of the Nervous System

• Peripheral Nervous System• Cranial nerves• Spinal nerves• Somatic nerves• Autonomic nervous system

• Sympathetic• Parasympathetic

Neurological disordersCranial Nerves

Cranial Nerves

Cranial Nerves Reviewed

Autonomic Nervous System

Neurological disorders

• Cells of the Nervous System• The Neuron• Neuroglia and Schwann cells

• The Nerve Impulse• Synapses• Neurotransmitters

• Myelin Formation:• Peripheral NS – Schwann cells• Central NS – Oligodendrocytes

Neuron

Neuroglia

Saltatory Conduction

http://s3.amazonaws.com/ppt-download/nerve-impulse-28770.ppt#256,1,NERVE IMPULSE/ACTION POTENTIAL

Web Site with AP transmission animation

The Synapse

The Brain

The Brain (Functional Areas)


• Protective structures• Cranium• Meninges• Cerebrospinal fluid and the

ventricular system• Vertebral column• Blood supply


The Meninges

Cerebral Ventricular System

MRI of Spinal Cord within Vertebrae

Cerebral Blood Supply

Circle of Willis

PainA Summary of Important Concepts

Part II

Pain

Pain (definitions)

• Pain Threshold – point at which a stimulus is perceived as pain

• Pain Tolerance – amount of pain a person will tolerate before outwardly responding to it

• Nociceptive pain – pain resulting from direct tissue injury

• Non-nociceptive pain – neuropathic pain

Neuropathic (non-nociceptive pain)


• Pain (continued)• Acute versus chronic pain

• Acute pain is a protective mechanism

• Chronic pain is persistent, lasting > 6 months


• Clinical manifestations of pain• Acute pain

• Somatic pain• Visceral pain• Referred pain

• Chronic pain• Neuropathic pain• Hyperesthesias• Phantom limb pain• Cancer• Reflex sympathetic

dystrophy(RSD)

Referred Pain

Alterations in Neurological FunctionPart III

Neurological Disorders• Alterations in Cognitive Systems

• Alterations in arousal – Coma • Structural vs. metabolic vs. psychogenic

causes• Grouped according pathologic process

• Infectious• Vascular• Neoplastic• Traumatic• Congenital• Degenerative• Polygenic• Metabolic

Coma

• By definition, coma (decreased arousal) is produced by:• Bilateral hemispheric damage• Suppression by hypoxia,hypoglycemia,

drugs or toxins• Brain stem lesion or metabolic

derangement that suppresses Reticular Activating System (RAS)


• Coma• Clinical manifestations

• Level of consciousness• Pattern of breathing (cheyne-stokes)• Pupillary changes• Oculomotor responses (ie. Doll’s

eyes)• Motor responses

Posturing

• Decorticate• Flexion of arms, wrists, fingers• Adduction of upper extremities• Extension of lower extremities

• Decerebrate• Extremities in extension• Pronation of forearms and plantar

extension of feet

Decorticate ->

<- Decerebrate

Glasgow Coma Scale (GCS)


• Outcomes• Mortality

• Brain death – brain stem death – no potential for recovery –no control of homeostasis

• Cerebral death – death of cerebral hemispheres not including the brain stem – vegetative state

• Morbidity • Recovery of consciousness• Residual cognitive dysfunction• Psychosocial domain• Vocational domain


• Seizures – a sudden, explosive disorderly discharge of cerebral neurons

• Characterized by sudden, transient alterations in brain function

• Clinical manifestations – Motor, Sensory, Autonomic, Psychic, Level of arousal

• Epilepsy – term applied to seizures in which no underlying cause is found

• General term for primary condition causing seizures


• Conditions associated with seizure disorders

• Any disorder that alters neuronal environment

• Metabolic defects• Congenital conditions• Genetic predisposition• Peri- or post-natal injury• Infections• Tumors• Drugs or alcohol


• Terminology• Aura• Prodroma• Tonic phase• Clonic phase• Postictal state

Generalized Seizures• Generalized Seizures • (Produced by the entire brain) Symptoms • 1. "Grand Mal" or Generalized tonic-clonic

Unconsciousness, convulsions, muscle rigidity

• 2. Absence Brief loss of consciousness • 3. Myoclonic Sporadic (isolated), jerking

movements • 4. Clonic Repetitive, jerking movements • 5. Tonic Muscle stiffness, rigidity • 6. Atonic Loss of muscle tone

Partial Seizures• Partial Seizures • (Produced by a small area of the brain) Symptoms • 1. Simple (awareness is retained)• a. Simple Motor• b. Simple Sensory• c. Simple Psychological a. Jerking, muscle rigidity, spasms,

head-turning• b. Unusual sensations affecting either the vision, hearing, smell

taste or touch• c. Memory or emotional disturbances • 2. Complex • (Impairment of awareness) Automatisms such as lip smacking,

chewing, fidgeting, walking and other repetitive, involuntary but coordinated movements

• 3. Partial seizure with secondary generalization Symptoms that are initially associated with a preservation of consciousness that then evolves into a loss of consciousness and convulsions.

Neurological disorders• Types of seizure disorders

• Generalized seizures• Partial seizures• Status epilepticus • Absence• Pseudo-seizures

• Treatment of seizure disorders• Medications• Patient education• surgery


• Data processing defects• Agnosia – failure to recognize form

and nature of objects• Dysphasia – impairment in

understanding or production of language

• Expressive• Echolalia

• Aphasia – loss of ability to understand or produce language


• Dementia

• Progressive failure of multiple cerebral functions

• Syndrome with many causes

• Loss of intellect with impaired mental abilities

• Disoriented

• Memory problems (recent and remote)

• Language problems

• Attentional focus

• Alterations in behaviors


• Evaluation of cause• Neuropsychological testing• Laboratory and diagnostic testing

• Treat underlying cause• Infections• Nutritional issues

• Progressive dementias• Goal is to maintain current

function and prevent continued deterioration

Neurological disorders• Alzheimer disease (AD)

• Most common cause of severe cognitive dysfunction in older persons

• Familial, early-onset – occurs in persons before age 65

• Familial, late-onset – known as FAD• Non-hereditary, late-onset AD – occurs in 70% of

cases• Exact cause is not known – several theories

• Loss of neurotransmitter stimulation by choline acetyltransferase

• Mutations in genes that code amyloid proteins• Alterations in apolipoprotein E (binds beta

amyloid)• Neurofibrillary tangle• Senile plaques – diagnostic of Alzheimer’s Disease• Diagnosis• Treatment

Alzheimer’s Atrophy

Pet Scan and AD

Alzheimer’s Disease Microscopic Pathology

Neurological disorders:Trauma and Bleeds

• Hematomas• Extradural hematomas• Subdural hematomas• Subarachnoid hemorrhage• Intracerebral hemorrhage

Epidural Hematoma

Subdural Hematoma

Subarachnoid Hemorrhage

Intracerebral Hemorrhage

Neurological disorders• Cerebrovascular accidents (Stroke)

• Occurs in 600,000 persons per year• Third leading cause of death in US• Most common in persons > 65 years• More common in women• More common in African-Americans and Asians• Heredity component

CVA on CT

Neurological disorders• Risk factors for CVA

• Hypertension• Smoking• Diabetes• Insulin resistance• Polycythemia and thrombocythemia• Elevated lipoprotein-a• Impaired cardiac function• Hyperhomocysteinemia• Atrial fibrillation• Estrogen deficiency

Carotid Artery Disease

Carotid Artery Disease

Neurological disorder• Thrombotic strokes

• Due to arterial occlusion caused by thrombi• Classified secondary to clinical manifestations

• Transient ischemic attacks (TIA)• Caused by thromboembolic particles • Abrupt onset of symptoms

• Strokes-in-evolution (Sometimes called RIND –reversible ischemic neurologic deficit)

• Intermittent progression of neuro deficits over hours to days

• Completed strokes• Maximum amount of destruction has

occurred

Neurological disorders• Embolic strokes

• Fragment of clot breaks off from thrombi outside of brain

• Most common from heart, aorta, carotid artery or thorax

• Risk factors atrial fibrillation, MI, endocarditis, valve replacements

• Tumors, fat and air can also cause strokes

• Hemorrhagic strokes• Third most

common cause of CVA

• Risk factors• Hypertension• Aneurysms • Bleeding

disorders• Tumors • Trauma • Drug use


• Symptoms of CVA• Depend upon which artery is obstructed

• Weakness• Facial drooping• Loss of or trouble with speech• Loss of function of limbs – hemiparesis• Loss of or changes in vision• Headache• Inability to recognize objects or persons• Changes in level of consciousness


• Treatment of CVA• “Time is Brain” treatment within 6 hours of

onset of symptoms• Interventional and drug therapy

• Clot busters – thrombolytics – TPA • Improve blood flow - vasodilators• Stenting of vessels• Prevention of thrombus – anti-platelet drugs

• Physical, emotional and mental rehabilitation• Education of patient and family

Aneurysms

• Many etiologies (can be inherited)• Dilation or outpouching of vessels• Usually go undiagnosed until they bleed• Treated surgically

Aneurysm

Aneurysm Clip

Neurological disorders• Headaches – Most common neurological disorder

• Can be a symptom of serious illness• Can be a symptom of being a nursing student

• Migraines - Benign recurring headache provoked by a trigger• Affects 11 million person in the U.S.• Prevalent in women ages 15-55 years and can

occur in children• Auras can occur• Most common is migraine without aura

Tension Vs. Migraine Headaches

• Symptom A• TensionB• Migraine• Intensity, Duration and Quality of Pain• Mild or moderate pain intensity √ √• Severe √• Duration of headache • 30 min – 7 days• 4-72 hours √• √• Intense pounding, throbbing and/or debilitating

√

SymptomATension

BMigraine

Intensity, Duration and Quality of Pain

Mild or moderate pain intensity √ √

Severe √

Duration of headache 30 min – 7 days 4-72 hours

√ √

Intense pounding, throbbing and/or debilitating √

Distracting but not debilitating √

Steady ache √

Location of Pain

One side of head √

Both sides of head √ √

Associated Symptoms

Nausea/vomiting √

Sensitivity to light and/or sounds √

Aura before onset of headache such as visual symptoms √

Neurological disorders• Basis of migraines is multifactorial

• Serotonin• Vasoactive substances• Inflammatory processes

• Treatment of migraine• Avoidance of triggers• Rest or sleep in a dark, quiet room• Compresses, cold or warm• Medications

• Serotonin antagonists (Imitrex)• Beta or calcium channel blockers• Aspirin, caffeine, NSAIDS• Magnesium supplements

Migraine On MRI


• Meningitis – infection & inflammation of meninges• Caused by bacteria, viruses, fungi, parasites or

toxins• Acute, subacute or chronic

• Bacterial vs. aseptic meningitis• Symptoms

• Fever, chills, petechial rash• Headache, photophobia, otophobia, neck

stiffness• Nuchal rigidity, decrease consciousness,

seizures, hemiparesis, hemiplegia

Meningitis


• Treatment • Supportive measures - Quiet, dark

room• Antibiotics or anti-viral medications• Vaccinations are available for

bacterial form• Chemoprophylaxis for exposed

persons


• Parkinson’s disease• Common degenerative disease of basal

ganglia involving the dopamine-secreting cells

• Onset after age 40, most common in men

• Primary vs. secondary

Degeneration of the Substantia Nigra

NORMALParkinson’s Disease


• Symptoms• Resting tremor• Rigidity• Akinesia – hypokinesia and

bradykinesia• Stooped posture• Shuffling gait, equilibrium disorders• Orthostatic hypotension,

gastric/urinary retention and constipation

• Depression


• Treatment• Administration of dopaminergic drugs -> L-

Dopa• Antihistamines, amantadine reduce akinesia• Drugs lose effects over time• Stem cell research

• Slow, progressive disease• Total loss of function• Death is commonly due to pneumonia

Neurological disorders• Multiple sclerosis (MS)

• Common immune disorder involving CNS• Demyelinating disorder

• Onset between 20 and 50 years• Females affected twice as often as males• Most prevalent in northern countries• Genetic susceptibility

• Previous viral insult in a genetically susceptible person T cells reactive to myelin

• Destruction of myelin leads to slowing and eventual blockage of conduction

MS on MRI


• MS (continued)• Different types of MS

• Mixed, spinal, cerebellar, amaurotic forms

• Different clinical courses• Relapsing-remitting• Primary progressive• Secondary progressive• Progressive relapsing


• MS (continued)• Symptoms

• Optic neuritis• Visual changes• Dizziness• Nystagmus• Weakness• Numbness, tingling• Ataxia, tremor• Bladder and bowel changes

Neurological disorder• MS (continued)

• Diagnosis with CT scan or MRI• CSF exam• Treatment

• Acute management of exacerbations• Reducing frequency of relapses or disease

progression• Steroids• Interferon• Immunosuppressive agents• Symptom management• Physical and occupational therapy• Patient education• Support of patient and family

Intracranial Neoplasms

• 50 – 60% of all adult intracranial neoplasms are malignant gliomas and/or astrocytomas

• Approximately 25% of patients with primary tumors outside of the CNS will develop intracranial metastases. Most of these develop secondary to lung cancer.

Glioblastoma on MRI

Glioblastoma on MRI

GLIOBLASTOMA

Cerebral Edema

Elevated Intracranial Pressure (ICP)

• Medical Emergency• Symptoms include headache, vomiting

and changes in LOC• Medically treated with mannitol and other

agents• Definitive treatment involves correction of

underlying pathology• Complications include herniation

Health & Medicine

Neuropathology