neurology review
TRANSCRIPT
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
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
…..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
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