NEUROLOGY REVIEWJames K. Rustad, M.D. Copyright © 2010. All Rights Reserved.

Lecture Outline

Neuroanatomy Review Neurotransmitters: Dopamine,

Norepinephrine, Serotonin Pain: Peripheral Nerve Fibers, Opiate

Receptor Subtypes and Neuropathic Pain Syndromes

Headaches (Tension, Migraine, and Cluster Headaches)

Brain Hemorrhages (Subdural, Epidural and Subarachnoid Hemorrhages)

Lecture Outline

Dementias: Alzheimer’s, CJD, Lewy Body, Pick’s, NPH, SSPE

Neuropathology “power review”: Parkinson’s, Huntington’s, Duchenne’s, ALS, Guillian Barre, Myasthenia Gravis, Multiple Sclerosis, Seizure Disorder, and Brown-Sequard Syndrome.

Stroke Lesion Localization Aphasias

Neuroanatomy Review

Frontal Lobe: Remember stimulation drives eyes contralateral and destruction induces ipsilateral eye movement. Prefrontal Region - Frontal lobe anterior to motor strip contains executive and inhibitory centers.

Parietal Lobe: Stereognosis, two-point discrimination, visual association area (perception of visual symbols). Angular Gyrus (Gerstmann’s syndrome).

Occipital lobe: Visual cortex. Temporal lobe: Wernicke’s area. Mesial surface

is origin of most partial complex seizures.

Neuroanatomy Review (continued)

Basal Ganglia = Caudate nucleus, Putamen, Globus Pallidus, Subthalamic Nucleus, Substantia Nigra.

Striatum = caudate nucleus and putamen.

Lenticular Nuclei = globus pallidus and putamen.

Nigrostriatal tract (substantia nigra to striatum).

Dopamine Metabolism StepsPhenylalanin

eTyrosine DOPA

Dopamine

Norepinephrine

Phenylalanine

Hydroxylase

Tyrosine Hydroxyla

se(rate-

limiting) DOPA Decarboxyl

ase

Dopamine Beta

HydroxylasePhenylamine

N-Methyltransfe

rase

Epinephrine

Serotonin Synthesis

Serotonin

Breaks down to 5-HIAA (5-Hydroxyindoleacetic acid)

5-hydroxytryptophan

Converted by: Amino acid Decarboxylase

Tryptophan

Converted by: Tryptophan Hydroxylase

Peripheral Nerve Fibers, Opiate Receptor Subtypes and Neuropathic Pain Syndromes

Pain

Peripheral Nerve Fibers

Type C fibers A-delta fibers

Size Small Large

Myelin No Yes

Conduction Velocity Slow Fast

Character Dull, aching Sharp, brief

Example Pancreatic cancer Burn

Opiate Receptor SubtypesReceptor Action

Mu Analgesia, respiratory depression, constipation, miosis (pupillary constriction), euphoria

Kappa Analgesia, dysphoria, disorientation/depersonalization

Delta analgesia

Neuropathic Pain Syndromes Mononeuropathy: Carpal tunnel

syndrome Polyneuropathy: Diabetic, Alcoholic Post-herpetic neuralgia

Neuropathic Pain Syndromes Complex Regional Pain

Syndrome Type I (Reflex Sympathetic Dystrophy)

Initial noxious event involving distal extremity, pain disproportionate to injury, not limited to single nerve distribution.

Associated with edema, changes in skin blood flow.

Neuropathic Pain Syndromes

Sequela of injury to nerve or major branch (esp. median, sciatic, tibial, and ulnar nerves).

Due to thalamic infarct or other lesion.

Hemi-anesthesia followed by gradual return of sensory function and pain.

Pain contra-lateral to lesion.

Complex Regional Pain Syndrome Type 2 (Causalgia)

Thalamic Pain: Dejerine-Roussy Syndrome

Headaches

Headaches

Tension headache

Dull, bilateral, band like, chronic in course and usually related to stress.

Tx: NSAID, rule out Major Depression

Migraine: at least five episodes of Episodic Headache lasting four to seventy two hours

Unilateral Throbbing Worsened by

movement Moderate or

Severe

Nausea or vomiting

Photophobia and phonophobia

Any two of: Any one of:

Five Phases of Migraine Attack Phase I: Prodrome Phase II: Aura Phase III:

Headache Phase IV:

Headache Resolution

Phase V: Postdrome

Migraine Treatments

Non-specific: NSAIDS, Combination analgesics, Opioids, Antiemetics, Neuroleptics.

Specific: Ergotamine, Dihydroergotamine, Triptans.

Anticonvulsants (Divalproex, topirimate)

Tricyclics Beta-Blockers Calcium Channel

Blockers

Acute Preventive

Cluster Headache

M/F 6:1 Unilateral

stabbing headache

Ipsilateral lacrimation and nasal congestion with rhinorrhea

Usually triggered by alcohol use.

Treatment: 100% Oxygen (“Air Supply”)

Cluster Headache

Rare Disorder (0.1-0.4% of population) Age of onset 20’s-30’s Clinical features: Excruciatingly severe,

retro-orbital pain. Radiates to temple, teeth, neck. Last 15-180 minutes.

Ipsilateral autonomic features, pacing, nocturnal attacks often awaken them.

Triggers: Alcohol, Nitroglycerin. Cycles usually occur spring and fall and

last 4-12 weeks.

Cluster Headaches

Oxygen 5-10 Liters

Sumatriptan injection (FDA approved)

Ergotamine

Prednisone Verapamil Lithium (for

chronic cluster headaches)

Divalproex

Acute Preventive

Subdural, Epidural and Subarachnoid Hemorrhages

Brain Hemorrhages

Subdural Hematoma

Suspect in older patient with new-onset headache

Follows head trauma Tearing of bridging

veins Extra-axial mass

causes focal findings

Waxing and Waning mental status

“Concave on CT”

Epidural Hematoma

Between bone and dura

Associated skull fracture in 85% of adults

Middle meningeal artery tear

Brief LOC, initial lucid period then acute deterioration

“Convex on CT”

Subarachnoid Hemorrhage Cause: Rupture of

aneurysm or AV malformation. Clinical feature: sudden onset of “worst headache of my life”

Studies: CT scan. LP will show blood and Xanthochromia (yellow heme pigment)

Tx: Clip aneurysm

“Athena and Zeus”

Subarachnoid Hemorrhage Occipito-nuchal Sentinel bleeds Most common

cause? Trauma

Dementias

Alzheimer’s Disease

Extracellular deposition of amyloid-beta protein, intracellular neurofibrillary tangles, and loss of neurons.

CT: Atrophy, ventricular dilatation

Treatment:

CJD vs. AD

CJD AD

Course Six months (rapid) Insidious (years to decades)

Physical findings Myoclonus

EEG Periodic complexes, burst-suppression

Slowing of background

CSF 14-3-3 protein (>90%), some false +

Pathology Spongiform changes Plaques and tangles

Transmissibility Person to person and person to animal

Non-transmissable

Huey, Dewey and…

…..Lewy Body Dementia

2nd commonest cause of degenerative dementia

Progressive cognitive impairment

Spontaneous onset Parkinson’s symptoms

Extreme neuroleptic sensitivity, Sleep problems, V/H

Pick’s disease

Personality change Decline in function Poor social

judgment Inappropriate Pathology:

Prominent fronto-temporal atrophy, neuron cell inclusions, clustered cytoskeletal elements

“NPH wouldn’t do that!”

Triad: an imbalanced, wide-based walk or “shuffle,” urinary incontinence and MEMORY PROBLEMS.

Dementia predominantly frontal lobe in nature, with apathy, dullness in thinking, and slight inattention. Memory problems are usually main problem, which can lead to the misdiagnosis of AD.

Neil Patrick Harris, aka “Doogie Howser, MD”

Normal Pressure Hydrocephalus Dementia Incontinence Gait apraxia

(“magnetic gait”)

Subacute Sclerosing Pancephalitis (SSPE)

Dementia and myoclonus with onset in childhood

Course usually rapid and fatal, may be aborted with antiviral drugs

CSF has anti-measles antibodies, and EEG shows periodic or burst-suppression

Cause probably measles or measles-like virus

Parkinson’s, Huntington’s, Duchenne’s, ALS, Guillian Barre, Myasthenia Gravis, Multiple Sclerosis, Seizure Disorder, and Brown-Sequard Syndrome.

Neuropathology “power-review”

Parkinson’s Disease

Tremor: resting, “pill-rolling,” coarse, 3-5 Hz.

Rigidity: “cogwheel”

Bradykinesia or akinesia

Festinating gait: small accelerating steps with decreased arm swing.

Postural reflex abnormalities including a positive “pull test”

Hypophonia, Micrographia

Sleep Disturbances (partly iatrogenic from dopamine agonists)

Cardinal Features Minor Features

Huntington’s Disease

Atrophy of cerebral cortex and head of caudate nuclei leads to compensatory enlargement of lateral ventricles (“bat-wing”).

Excessive Cytosine-Adenine-Guanine (CAG) trinucleotide repeats (other illnesses with excessive trinucleotide repeats include: Myotonic dystrophy, Fragile X syndrome, many forms of Spinocerebellar degeneration).

Duchenne’s Type Muscular Dystrophy

Sex-linked recessive inheritance with onset in early childhood

Caused by loss of muscle membrane protein, dystrophin

Pseudohypertophy (especially in calves) Proximal weakness: requires arms to arise

from chair or floor DTRs decreased except for Achilles reflexes

(ankle) Elevated muscle enzymes: CPK, aldolase

UMN vs. LMN

Sign and Symptoms

Upper Motor Neuron

Lower Motor Neuron

Reflexes Hyperactive Hypoactive

Babinski sign Positive (dorsiflexion) Negative

Muscle atrophy Absent Present

Muscle tone Spasticity Flaccidity

Fasciculation Absent Present

Amyotrophic Lateral Sclerosis Combines UMN and

LMN symptoms Asymmetric limb

weakness = most common presentation. Limb fatigability, twitching, wasting, and stiffness.

Bulbar onset (2nd most common type) features dysarthria and dysphagia.

“Lou Gehrig’s disease”

Clinical Case ScenarioA patient develops progressive weakness two weeks after a viral infection. What is possible diagnosis and what tests would you order?

Acute Idiopathic Polyneuropathy “Guillain Barre Syndrome”

Guillain-Barre

Symmetric weakness, usually beginning in the legs, and more marked proximally than distally.

Some sensory complaints. Typical absence of deep tendon reflexes. May

be marked autonomic dysfunction. Slow conduction velocity CSF shows increased protein concentration

but normal cell count. Electrophysiology shows marked slowing of motor/sensory nerve conduction velocity (denervation and axonal loss)

Guillain-Barre

Treatment: Plasmapheresis or IV IG

Myasthenia Gravis

Insidious onset. Slowly progressive course.

Diplopia, dysarthria, ptosis, extremity and generalized weakness not conforming to distribution of any single nerve.

Pupillary responses not affected. Persistent activity of a muscle

group leads to temporary increase of weakness > restoration of strength after brief rest.

Myasthenia Gravis

Edrophonium challenge test (screening)

EMG Confirmatory: Ach receptor antibody

test Tx: Neostigmine, Pyridostigmine (if

poor response: Corticosteroid). Consider Thymectomy in all patients

< 60 yr unless only extraocular weakness.

Multiple Sclerosis

Relapsing remitting symptoms

Separated in space and time

MRI: Multiple periventricular plaques in white matter.

Oligoclonal bands in CSF.

Internuclear ophthalmoplegia When the

patient attempts to look to left, left eye turns with nystagmus (abducted eye) and right eye cannot turn to left (impaired adduction).

Location of lesion: Medial longitudinal fasciculus.

Young adults: MS most common cause

Older patients: vascular diseases.

Seizure Disorder

Partial Seizures: originate in a focal region of a single hemisphereSimple Partial Seizures: no alteration of consciousnessSecondary Generalization: spreads to both hemispheresComplex Partial Seizures: alteration of consciousnessBrief Duration (i.e. 2-3 minutes); May have motionless staring or automatisms (involuntary motor behaviors)

Generalized seizures: involve both cerebral hemispheres from the outset

(1). Tonic: sudden muscular rigidity (extension or flexion) (2) Clonic: generalized rhythmic jerking of muscles, no initial tonic phase (3) Generalized tonic clonic (may feature epileptic cry, apnea/cyanosis). Ictal activity 1-2 min; Post-ictal: incontinence, flaccidity, gradually return to normal consciousness. Disoriented, headache, sore mouth (oral trauma, muscular ache)

(4). Atonic Seizure: brief loss of muscle tone(5). Absence ("petit mal") a few seconds of staring/blank look/unresponsive(6). Myoclonic: localized or widespread: non-rhythmic rapid jerking movements of muscles

Brown-Sequard Syndrome Contra: loss of P and T, Ipsi: loss of

vib./joint position, paralysis, hyperreflexia, Babinski

CSF in Meningitis

Diagnosis Cells Glucose (mg/dl)

Protein (mg/dl)

Opening Pressure

Normal 0-5 lymphocyte

45-85 15-45 70-180

Aseptic,viral

25-2000, mostly lymphocytes

NORMAL High > 50 Slight elevation

Bacterial 200-20,000 Polymorphs, neutrophils

Low <45 High >50 Markedly high

Tuberculosis

100-1000 lymphocytes

Low <45 High > 50 Moderate Elevation

LOCALIZATION OF STROKES

The Circle of “whatchu talkin’ bout” Willis?

Anterior Cerebral Artery

Profound lower extremity weakness (contralateral)

Stroke may result in paralysis/sensory loss in contralateral leg and foot.

Middle Cerebral Artery

Profound upper extremity weakness (contralateral).

Contralateral hemiplegia, hemisensory loss and homonymous hemianopia, eyes deviated to side of lesion. Apraxia/neglect. If left lobe involved: Global aphasia.

Posterior Cerebral Artery

Contralateral homonymous hemianopia, with macular sparing.

Prosopagnosia (inability to recognize faces)

Vertebrobasilar Artery

Vertigo Nausea and

vomiting “Drop Attack” Vertical

Nystagmus Dysarthria/

dystonia Ataxia Labile Blood

Pressure

Posterior inferior cerebellar artery Lateral Medullary or Wallenberg’s

syndrome Sensory loss of the “FACE” 9 and 10 C.N. damage Limb ataxia Horner’s syndrome Spinothalamic sensory loss

Pure Motor Stroke

Weakness of face, arm, and leg on one side of body (without cognitive, sensory, visual abnormalities) favors presence of thrombotic stroke involving penetrating arteries or small intracranial hemorrhage.

Gerstmann’s Syndrome

Finger agnosia Left-right

disorientation Agraphia Acalculia

Dominant parietal lobe angular gyrus lesion (stroke or congenital abnormality).

Associated with learning disabilities, right-sided paresis and hyperactive DTR’s.

Category Non-fluent Aphasia Fluent Aphasia

Previous terms (not synonymous)

Expressive, Motor, Broca’s, Anterior

Receptive, Sensory, Wenicke’s, Posterior

Spontaneous Speech Output: Sparse < 50 WPM, single wordsContent: Nouns and Verbs primarily, Dysarthric, Telegraphic

Output: Plentiful > 100 WPM, entire phrases, Paraphasias (incorrect words, clang associations, neologisms)

Response to Tests Comprehension Preserved but Naming and Repeating impaired

Comprehension Impaired (variable) and Naming and Repeating impaired

Associated Deficits R-sided hemiparesis (arm > leg)

Minimal hemiparesis, hemianopia, hemisensory loss

Etiology CVAs, trauma, other focal lesions

Focal lesions, sometimes frontotemporal dementia, AD, cerebral anoxia

Location of Lesion Frontal lobe, especially L MCA

Temporal or parietal lobe

Variants of Fluent Aphasia

Conduction Transcortical (Isolation)

Abnormality Cannot repeat Can only repeat (echolalia), other functions variable

Nature of Injury Disconnects arcuate fasciculus

Isolates language arc from remainder of cortex

Etiology Focal lesions Anoxia, CO poisoning, occasionally AD

Location of lesion Posterior temporal lobe

Area(s) surrounding peri-sylvian arc

Any questions?