Diseases of Peripheral n (neuropathies)

Age of Location of Pathogenesis Clinical Presentation Gross/Micro

Onset Lesion Pathology
Diabetic Adult-onset Symmetric distal Segmental Decreased sensation in distal Axonal neuropathy
Peripheral polyneuropathy demyelination extremities Segmental
Neuropathy demyelination,
thickening of
endoneurial arterioles,
hyalinization
Werdnig- At birth or Degeneration of Autosomal recessive LMN lesion; gen weakness, Atrophy of ventral
Hoffman w/in 1st 4 LMN Mutation in SMN1 hypotonia, m wasting, tongue horns/n roots;
Disease months (missing exon 7) fasciculations; floppy baby neurogenic atrophy
(SMA type I)
Amyotrophic Middle UMN & LMN Autosomal dominant UMN lesion deficits (hyperreflexia, Atrophy of ventral
Lateral aged/elderl Degeneration of LMN Babinski) LMN lesion (fasciculations, horns/n roots; Wallerian
Sclerosis y and UMN wasting, weakness) degen
Guillain-Barre Degeneration of Immune-mediated Ascending paralysis; weakness in Chronic inflammation,
Syndrome peripheral nn disorder distal limbs w/ rapid advance to seg demyelination
proximal mm, slow n conduction
Charot-Marie- Childhood, Degeneration of Autosomal dominant Distal m weakness; inverted Onion bulb-Segmental
Tooth early peripheral nn Chromosome 7 champagne-like calf; pescavas, demyelination-
(HSMN type 1) adulthood duplication; PMP 22 hammertoes remyelination;
Neurogenic atrophy: atrophy in m fibers due to pathological changes in n or PNS
Denervation atrophy: myocytes atrophy due to axon/myelin sheath degeneration
Wallerian degeneration: axonal degeneration distal to point of axonal damage or cell body damage
Disease of NMJ
Myasthenia NMJ Immune-mediated Begins with extraocular m
Electrophysiological
Gravis loss of Ach receptors weakness; ptosis, double vision;
tests: nerve
generalized weakness conduction and
electromyography; n/m
biopsy
Myopathies: have elevated creatine kinase and proximal weakness; random necrosis and/or m fiber regeneration
Neuropathies: distal weakness; group atrophy; fiber type grouping
 Increased Intracranial Pressure and Herniation
Etiology Compression Clinical Features
Increased ICP Depends on age of pt and speed of expansion Headache, vomiting, pailledema maybe (swollen optic n), abducens n.
Factors depend on speed of expansion, age of palsy
patient; >200mm water in LP Blurred optic discs; focal neurologic signs: limb weakness
Cingulate gyrus Herniates under the falxcerebri
Herniation
Uncal Hemorrhage, Uncus herniates across Ptosis, dilated pupil, fully abducted eye, fixed pupil, infarct of unilateral occ
Herniation neoplasms, tentorium cerebelli -compress lobehomonymous hemianopsia/hemianopia; Duret hemorrhages due to
infections structures in post fossa; downward brainstem compression
Compress PCA, midbrain Brainstem compression: central herniation or rostrocaudal deterioration
cerebral peduncle, CN III,
brainstem downward
Cerebellar Cerebellar tonsil herniation thru foramen Compresses medullary respiratory centers leading to death
Tonsil magnum
Herniation
Midline shift Lateral displacement of diencephalon may produce decreased level of consciousness
Central Supratentorial Small reactive pupils (loss of sympathetic), Dilated, fixed (loss CNIII parasympathetics because the
Herniation space parasympathetics travel in the PERIPHERY of CNIII), Midposition, fixed: compression of both III and
Rostrocaudal occupying midbrain (loss of sympa/para)
deterioration mass; Duret hemorrhages may also occur
downward Changes in consciousness (drowsiness, stupor, coma), resp changes; postural changes: Decorticate rigidity
displacement of (leg extension/arm flexion);
brainstem Decerebrate rigidity (leg/arm extension)
*Cheyne-stokes in diencephalon
*Central neurogenic hyperventilation in midbrain
*Apneustic Respiratory in pons
*Ataxic Respiratory in medulla
* In infants, skull may expand and in elderly, brain may have atrophied due to old age, so may have more room for expansion.
Infections involving Nervous System
Etiologic Pathogenesis Clinical Features Spinal Notes
Agents Fluid
Changes
Epidural/Subdural Pyogenic Direct inoculation or spread from nearby Localized collection Complicatio
Abscess or Empyema bacteria: step, infection of pus ns:
 staph
Meningit Bacterial Homogenous Purulent exudate in SAS w/ Hydrocephalus, P Hydrocephal
is spread from body PMN, bacteria, vasculitis; edema ICP, glucose us
Pyogenous to brain; direct Edema, cellular infiltration seizures, protein Edema
inoculation, direct of CN/sp roots thrombosis, CN palsies
cells
spread abscess, CN palsies Thrombosis
Viral Aseptic Normal P
Brain
Acute Normal
Lymphocytic glc abscess
Seizures
protein
cells
Fungal Candidiasis, Exudate, mononuclear P
Chronic Cryptococcus, infiltrate, vasculitis glc
tubercle Granulomatous ptn
bacillus, T.
cells
pallidum
(syphilis)
Viral Encephalitis Depend on Meningoencephali Arthropod-bourne VE Perivascular
age, location of tis, Epidemic; 10% by arbovirus cuffing,
pt, time of year encephalomyelitis HSV Type 1 neuronal/hemorrha RBCs
Homogenous Tx w/ acyclovir, effect gic necrosis, present
spread after mood, memory, behavior microglial
viremia, spread HSV Type 2 nodules/proliferatio
along nn Meningitis or encephalitis n, inclusion bodes
Rabies
Negri bodies: inclusions in
pyramidal neurons of
hippocampus
VZV shingles
granulomatous arteritis
infarcts
CMV common in
opportunistic viral
pathogens in HIV pts
Poliomyelitis infect
 antierior horn neurons,
motor deficits, flaccid
paralysis
Intracranial Abscess Pyogenic Intracerebral inflammation called granulomas Progressive focal pressure
bacteria Homogenous spread; caused by acute bacterial deficits, gen signs , few
(Staph/strep) endocarditis, cyanotic congenital heart disease; of increased ICP cells,
Discrete lesions w/ liquefactive necrosis, with WBC/ptn
zone of fibrous tissue ; normal
glc
HIV-associated
CNS Meningovascu Infiltration of meninges & vessels by Meningitis, or
Syphilis litis lymphocytes/ plasma cells vascular occlusion;
similar to low-grade
meningitis or stroke
General Atrophy, loss of cortical neurons in frontal lobes, Mental changes,
Paresis gliosis, prolif microglial cells, perivasc progressing to
lymphocytes, spirochetes dementia,
headache
Tabes Dorsalis Inflammation of meninges in SAS/dorsal n roots; Lightening pains,
wallerian degeneration sensory deficits,
loss PT/MVP; argull-
robertson pupils
Progressive Multifocal In pts w/ Viral encephalitis Intellectual Normal Death in 2-6
Leukoencephalopathy associated Latent infection of polyomavirus in kidney/B deterioration and mos
immune lymphocytes dementia, visual,
supp/chronic Demyelination; inclusion oligodendroglia nuclei motor dx,
dis abnmvmts
SubacuteSclerosingPane Progressive Persistent but nonproductive infection of the Intellectual gamma Death in
ncephalitis (SSPE) encephalitis CNS by altered measles virus; inclusion bodies deterioration, globulin several
associated with in oligodendroglia, neurons, astrocytes, seizures, spasticity Ab titer years
altered perivascular cuffing, neuronal loss, gliosis, of limbs, against
measles virus demyelination progressive mealses
personality changes
CNS development dx, including malformations, perinatal brain injury, cerebral palsy
Pathology Causes Clinical Features Types Diagnosis
Cerebral Palsy Intraparenchymal Asphyxia, maternal Ataxia/athetosis, Spastic: increased m
Correctly diagnosed bet 12-
hemorrhage high bp. Diabetes, dystonia, paresis, tone; stiff/jerky mvmts
24 mos
originating in trauma, infarctions, spasticity Ataxic: decreased m-floppy/limp body OR
germinal matrix hemorrhages tone/ poor stiffness of arms/legs in 1st
coordination few mos
Athetoid: due to -no smile by 3 mos
hyperbilirubinemia;-poor head control at 3-4
cant hold selves mos
upright -no sit up by 8 mos
-difficulty standing at 12
mos
-inability to walk by 18-20
mos
Germinal Matrix Subependymal matrix hemorrhages; due to cerebral hypoxia between 25th and 35th week of gestation
Hemorrhage
(Intraparenchymal
)
Periventricular Infarcts occur in the periventricular white matter; cyst may form
Leukomalacia Chalky yellow plaques of discrete regions of white matter necrosis and calcification
Ulegyria Due to ischemic lesionssulci bear the burnt of injury thinned-out, glioticgyri
Cerebrovascular Diseases Epidural Hematoma Subdural Hematoma
Disease Location/Etiolog Pathogenesis Notes
y
Strok Ischemic 1% of head trauma Bilateral in 10% of
e Thrombosis admin; 4:1 male to cases; more common
Embolism female; rare b4 age 2 in elderly
Hemorrha & after age 60 Acute: Chronic:
gic Trauma, Infants,
SAH, ICH contusio elderly, dev
Hypoxic Pyramidal cells of Decreased bld flow, anoxic Man in barrel Death may occur 2-12 n over mos,
Encephalopathy hippo, pukinjie cells poisons (CO, CN, CS2, syndrome hours after injury; dementia
(border zone: of cerebellum, GP hypoglycemia) causes uncal herniation
watershed neu or dnwd
infarcts)
Focal Cerebral Atherosclerotic Gross Path: 6-12hrs: no lesion discerned. 48
Ischemia plaque formation, hrs: tissue pale, soft, swollen, gray-white matter
coagulability of jxn indistinct. 2-10 days: gelatinous, friable.
Thrombotic blood, vasc occl, 10d-3wks: tissue liquefies
ateriopathy, cerebral Micro Path: 12hrs: neu nuclear pyknosis,
Due to focal amyloid angiopathy, cytoplasmic eosinophilia; 1-3days: PMN, cap
cerebral arterial drug abuse, prom, endo swell, vacuolation of white matter.
occlusion aneurysm 3-5days: m appear. 7-21d: astrocytes
proliferate, gemistocytic
Pale Infarct Shrinkage, distortion of structures, cysts,
Non-hemorrhagic compensatory ventricular enlargement
Ischemic neu (eosinophilic/red neurons);
capillary prominence, vacuolation of white
matter, macrophages, astrocytes become
gemistocytic
Ischemia due to Sudden onset of focal Hemorrhagic infarction; Skull fracture rupture Shearing of bridging
Embolism impairment characterized by petechial of MMA-rapid bleeding veins; accum around
Thrombotic hemorrhages mass effect parenchymal
embolus in MCA laceration; 2 to acc-
deceleration injury
Venous or Dural Blood stasis in large vv/venous sinuses leads to infarction; increased Unconsciousness, lucid No lucid interval
Sinus Thrombosis pressure disrupts capillaries causing blood to enter infracted areas interval, coma, focal Nonlocalizing,
Spontaneous Hypertension; others Arteriolosclerosis ; thickening signs, ICP, death may headache, confusion,
INtraparaencymal are AV malformation, of vessels, hyalinization, form occur 2-12 hrs due to progressive neurologic
Hemorrhage ruptured aneurysm, of sm aneurysms; Charcot- herniation; deteriation
amyloid angiopathy, Bouchard Aneurysms obtundation, contra Chronic: seizures,
leukemia Uncal herniation-brainstem hemiparesis, ipsi headache, confusion,
--basal compression & 2 Duret pupillary dilation behave changes, signs
ganglia/thalamus brainstem hemorrhages of ICP
and pons and
cerebellum
Aneurysms Occur at bifurcations Rapidly developing severe Common cause Biconvex high density; Crescentic mass of
Berry/Saccular/ of vessels at base of headache of SAH sharply defined; rarely high attenuation, may
Congenital brain cross sutures, may cross sutures; do NOT
cross midline & cross midline; less
tentorium dense than EDH, but
 high density on CT
Vascula AVM Tangles of abnormal vessels Remove blood &
r Seizure, headache, focal neurological signs associated organization
Malform tissue
. AV Causes high output cardiac failure; generally involves vein of Galen and
Shunt MCA or PCA
Lacunes Infarcts Small infarcts, associated with HTN ; tissue loss with scattered lipid-
laden macrophages and surrounding gliosis
Slit Hemorrhages Rupture of penetrating arterioles small ICH resorption leaving slit-
like cavity
Hypertensive Rapidly evolving syndrome of severe HTN
Encephalopathy Headache, nausea, & vomiting

Seizures
Epidemiolog 3% of all ppl living to age 80 will be diagnosed w/ epilepsy; highest incidence in young children and elderly ; 70% well
y/ controlled w/ meds, 30% w/ intractable epilepsy
Demographi
cs
Etiology Newborn Asphyxia, intracranial hemorrhage, hypocalcemia, hypoglycemia, hyperbilirubinemia, water
intoxication, inborn errors of metabolism, trauma
Infancy Febrile (5 mos-5 yrs), CNS infection, trauma, congenital defects, inborn errors of metabolism
Childhood Trauma, CNS infection, arteriovenous malformation, congenital defects, tumor
Adolescence Trauma, CNS infection, tumor, arteriovenous malformation, drgus/alcohol
Early Adulthood
Late Adulthood Drugs/alcohol, trauma, tumor, vascular disease, degenerative disease, CNS infection
Generalized Seizures Partial Seizures
General No aura, postictal confusion (not in Simple: no alteration in level of consciousness, no postictal state
Features absence/myoclonic seizure); may have bowel or Complex: alteration (not loss) in LOC; may have aura, postictal
bladder incontinence, tongue trauma confusion
Clinical Tonic m. rigidity (extension or flexion) Motor Tonic or clonic, versive head or eye movements
manifestatio Clonic Gen. m. jerking activity Sensory Positive phenomena: parasthesias/dysesthesias,
ns/ visual halllucinations
course Tonic- Rigidity followed by jerking; ictal Autonomic Gustatory, olfactory, epigastric fullness, nausea,
Clonic scream; apnea may appear / pupillary changes
 Grand mal Visceral
Atonic Bried loss of m. tone fall or head Psychic Dj vu, jamais vu, depersonalization
Petit mal drop
Absence Staring spell 5-15 sec; provoked by
hyperventiliation (only in
childhood);
no postictal
Myoclonic Localized/widespread jerking
mvmts; infantile, juvenile
Diagnosis CT or MRI, EEG, hematology (CBC, electrolytes, Ca, Phosphate)
 Intracranial Neoplasms
Primary More in Usually Childre Pilocytic astrocytoma Cystic lesion with mural nodule of tumor; good prognosis;
Tumors adults than in supratentorial; n grade 1; in cerebellum
children can spread via ICP may Medulloblastoma Grade 4; usually in cerebellum; poorly differentiated
CSF, but no be only neoplasm; truncal ataxia, ICP; seeding thruout SAS;
spread sign Most common mitotically active prognosis: gloomy
beyond CNS present Ependymoma Mostly in 4th ventricle; due to ICP; solid tumor, true
ed ependymal rosettes
Retinoblastoma Sometimes bilateral, may extend to optic n; good
prognosis
Neuroblastoma PNS, often in adrenal gland; poor prognosis
Adult Gliom Astrocytomas Cerebral hemispheres; low grades=firm, white/gray, poorly
50-75% as Grade 2: diffuse circumscribed, infiltrates & distorts brn tissue; grade 3-4:
are Grade 3: well circumscribed, infiltrates widely, many colors due to
primary anaplastic hemorrhage, necrosis, &cysts
Grade 4:
glioblastoma
Oligodendroglio Often in cerebral hemispheres; fried egg appearance;
mas slow-growing tumor
Ependymomas Within skull are rare; often in lateral ventricles more
common in the spinal cord
Primary Brain Lymphoma From B lymphocytes in CNS to deep cerebral
hemispheresheadache, seizures; soft, multiple separate
nodules
Germ Cell Tumors Origin: ectopic germ cells; location: midline
(pineal/suprasellar region); good prognosis
Pineal Parenchymal Clinical effects: visual disturbances and headache
Tumors
Meningiomas Well-circumscribed mass, no invasion; whorls or sheets of
meningothelial cells, psammoma bodies
Metastat Frequently Spread via
ic multiple, CSF
Tumors distributed by
 volume,
supratentoria
l
Intra- Meningioma
Axial Metastasis
Tumors Schwannom
a
Neurofibro
ma
Extra- Astrocytom Grade 2: nuclear pleomorphism (solid, infiltrating, may Survival over 5 years is rare
Axial a show cystic change
Tumors Grade 3: plus mitotic activity
Grade 4: Glioblastoma: Necrosis with palisading, and/or
vascular endothelial proliferation; may show
hemorrhage
Ependymom Usually in spinal cord in adults (4th ventricle in children) Prognosis related to resectibility
a
Oligodendro Can be associated with loss of chromosome 1p and 19q
glioma
Metastasis
Diagnosi Always cranial MRI with gadolinium enhancement
s
Von- Mutation in tumor
HippelLi Multiple CNS hemangioblastomas
ndau Increased renal cell carcinoma
Syndrom
e
Hemangi Thin-walled vessels w/ vacuolated cells; cystic lesion with mural nodule usually in cerebellum; 10% of patients have polycythemia
oblasto when tumor cells make erythropoietin
ma
Neurofib Mutation in Chromosome 17; peripheral neurfibromas may show malignant degeneration; pilocyticastrocytomas (optic nerve)
romatosi
sI
Neurofib Multiple meningiomas& bilateral acoustic schwannomas, ependymoma, mutation on chromosome 22-merlin protein
romatosi
s II
Tuberous Cortical tubers, angiomyolipoma of kidney, renal cell carcinoma, renal/hepatic cysts
Sclerosis

Disease Clinical Features
Hypokinetic Movement Disorders
Parkinson Rigidity, gait instability,
Disease resting tremor, bradykensia
--mood dx, later dementia,
dysautonomia
--olfactory dysfxn,
constipation, autonomic,
dysfxn, sleep dx,
dep/anxiety
Hyperkinetic Movement Disorders
Tremor Repetitive rhythmic alternating contractions of agonistic/antagonistic muscles: terminal, resting, postural/action, wing-beating
Movement Disorders
Pathology Epidemiology Differential Diagnosis
Degeneration of 11/100,000 in general Secondary Drug-induced, post-traumatic,
pigmented brainstem population Parkinsonis post-infectious, immune-
neurons in 50/100,000 over age m mediated, vascular, normal
substantianiagra, 50 pressure hydrocephalus
lewy bodies, Da in Cumulative lifetime Other Essential, myoclonic, dystonic
striatum risk: 2.7%; Slightly Tremor
more common in men Syndromes
Risk Factors: age, Akinetic- Progressive Supranuclear
severe head trauma, Rigid Palsy-
family history, env Syndromes Accumulation of hyper-
exposure, low uric acid phosphorylated tau ptn in
Protective factors: neuron-
estrogen, caffeine, CBT/CST signs, wide
heavy alcohol, unblinking face, axial rigidity,
smoking, NSAIDS dn gaze paresis
Multiple System Atrophy
Cerebellar signs,
dysautonomia, CST signs,
stridor
Corticobasal Degeneration
Progressive asymmetric
rigidity, apraxia, alien limb,
rarely gaze palsy
Diffuse Lewy Body Disease
Hereditary Wilsons: AR, deficient copper
disorders w/ excretion, serum/urine
Parkinsonis copper hepatic failure, basal
m ganglia- akinetic-rigid, wing-
beating tremor
Huntingtons
 tremor
Dystonia Sustained and/or phasic contraction of m causing abnormal posture or repetitive movements
Myoclonus Rapid, lightning-like m contraction producing irregular jerking
Chorea Brief, irregular jerking movements flowing from on body part to the next (metabolic, auto-immune, degenerative, vascular,
drugs)
Huntingtons Disease: expansion of CAG: chorea, dementia, psychiatric, cerebellar features, prominent atrophy of caudate
nuclei
Hemiballismus Rapid, large amplitude, unilateral, proximal flinging movements
Tics Repetitive, stereotypic, brief semi-involuntary movements

Demyelinating Diseases
Disease Age of Onset/ Etiology & Pathological Changes Diagnosis Treatment
Epi Pathogenesis
Multiple Sclerosis Age of onset: CD4 TH1, TH17 cells Initially: Optic neuritis MRI, CSF analysis : Ag non-selective
Autoimmune Dx 20-50; more react against self- Plaques of demyelination oligoclonal bands, IgG immunomodulato
common in myelin Ag & secrete in white matter of brain/sp CSF: gamma globulin rs : copaxone,
women and cytokines, B cells, T cd, not PNS; # of elevated, oligoclonal inhibits myelin
Caucasians cells, & innate immune oligodendrocytes, gliosis, gamma globulin bands basic protein
30-300/100,000 systemdemyelination activation of microglia and (MBP)
macrophages
Remitting and relapsing
Neuromyelitis Development of both optic neuritis and spinal cord demyelination at similar points in time
Optica (Devic Dis)
Acute Rapidly progressive diffuse demyelinating disease, develops 1-2 wks after viral infection
Disseminated Demyelination in perivenous distribution
Encephalomyelitis
Acute Necrotizing Common in young adults and children, usually in upper resp infection; CNS demyelination
Hemorrhagic
Encephalomyelitis
Central Pontine Demyelination in basis pontis and pontine tegmentum; classically associated with rapid correction of hyponatremia
Myelinolysis
Visual System Disorders
Three Vital Signs Visual acuity, Pupils, Pressure
Glaucoma
Optic Neuritis
Giant Cell Arteritis
Traumatic Optic neuropathy
Disease
Vertigo
Sensation of movement of
self/env, often rotary. Mismatch
of visual, vestibular, & sensory
proprioception
Concussion
Contussion
Diffuse Axonal Injury
Spinal Cord Lesions
Headache, jaw claudication, weight loss, malaise
A true neuro-ophthalmic emergency
Vestibular System Disorders
Clinical Central Causes
Features
Nystagmu Vertigo, diplopia, weakness, and/or
s, numbness
(hallmark) TIA not only vertigo, but combo of
diplopia, dysarthria, numbness,
incoordination
Tumor or mass rarely with isolated
vertigo; tx w/ traditional
prophylactic migraine meds
Migraine
Multiple Sclerosis important
cause
Nervous System Trauma
Etiology Clinical Manifestation
Trauma Transient acute
unconsciousness, headache,
cognitive and sleep
disturbances, vertigo
Trauma most Areas of hemorrhagic
common: orbital gyri, necrosis, Brain moves linearly
temp/occ pole or rotates, slam into skull
Trauma; present in Located in deep white matter
35% head trauma regions, Diffusion of tensor
deaths imaging
Blow to back of neck Sensory loss of sensation in a
Peripheral Causes
Vertigo, hearing loss, tinnitus
Benign Paroxysmal Positional Vertigo
Vestibular most common cause of vertigo; Dix-
Hallpike testing (pt rapidly moved from seated
position to lying position
Vestibular Neuritis monophasic episode of vertigo;
days to weeks, nausea/vomiting; tx w/vestibular
suppressants (meclizine, diazepam, Dramamine,
lorazpam)
Menieres Disease endolymphatic regulatory
dysfunction; last hours; ear pressure/fullness, change
in tinnitus & hearing function
Trauma
Notes
Not an anatomic lesion
No evidence of permanent structural damage
Coup lesions, counter coup, intermediary lesions
Major cause of prolonged traumatic coma, and poor
neurological outcome
Macrophages, gliosis, loss of architecture
(Direct v. Indirect) or trunk specific dermatone indicated Contusions, Wallerian degeneration
Trauma to C4, C5, C6, location of lesion
C7, T1 or T12, L1, L2
Headache
Epidemiolo Duration of Characteristics Locatio Treatment
gy Episode n
Tension Both 30 min-7 Progresses throughout day, no aura, Bilateral Regular meals, hydration, rest,
genders days no phonophobia/photophobia, no N/A, remove stress, anxiolytics
Age 20-60 pulsating, tightening, pressing, no
aggravation by exertion
Migraine Female No aura: 4- Can be with or w/o aura Unilater Abortive Preventive
Age 20-50 72 hrs Aura: N/V, photophobia, al NSAIDS, Anti-depressants,
Aura: 2 or phonophobia antihistamine anti-convulsants, -
more s, -adr adr blockers,
attacks blockers, neuroleptics
occ/supra-
orbital n block
Cluster Male Histamine mediated Unilater Ergotamines, Lithium,
Eye swollen and red, lacrimation, al lidocaine, topiramate,
ptosis, miosis, eyelid edema, nasal prednisone, ergotamine
congestion, rhnorrhea, facial 100% O2, verapamil, sodium
sweating sumatriptan valporate
Paroxysmal hemicrania Female No frank Horners syndrome; NSAIDS, salicylates
extremely responsive to Doesnt respond to O2
indomethacin
 Secondary Headaches
Vascular Sentinel bleed (AVM, SAH), stroke, arteritis, carotid/vertebral dissection, venous/sinus thrombosis, arterial
hypertension
Sentinel Thunderclap Headache: worst headache of life, ruptured aneurysm
Giant Cell (temporal) Older Achiness in jaw, neck, palpate artery, get sed rate, CRP
Arteritis patient
Trauma-associated Subdural hemorrhage, SAH, concussive, post-concussive
Intracranial Disorders Increased ICP w/ mass, benign intracranial HTN, intracranial infection, low ICP even
Metabolic Hypoxia, hypercapnia, hypoglycemia, dialysis; non-cephalic infection, facial pain
Cranial Neuralgias Trigeminal Neuralgia Severe pain in face, stabbing electric Tx: Carbamazepine, gabapentin, lamotrigine,
Tic Douloureux shock-like pain baclofen; Surgery: rhizotomy, microsurgical
2 to compression/inflammation of CN decompression, gamma knife
V
Glossopharyngeal Lancinating pain referred to tongue, Anticonvulsants, microsurgical decompression
Neuralgia ear
2 base of skull lesion, neck mass,
vasc compression
Occipital Neuralgia Aching pain, referred over scalp Unilater Anticonvulsants, occipital n branch
2 to cervical trauma, arthritis, C1-C2 al block, microsurgical decompression
Rebound Drug overuse, non-compliance, somatization, anger/anxiety, family Discontinue offending analgesics, EDUCATE,
dysfunction hydrate, preventive pharmacotheraphy
Toxic, acquired metabolic, and nutritional dx of the CNS
Source or Clinical Effects Notes
Deficiency
Lead Paints chips or CNS: in cerebral or cerebellar cortex
paint dust in -Acute: seizures, ataxia, ICP
Motor peripheral neuropathy homes -Chronic: seizures, attention/mental deficits, loss of motor
skills
PNS: in motor nn segmental demyelination; wrist-drop,
slowed n conduction
Mercury Vapor Inhaled dental Negligible
analgams
Methyl Fish Visual field constriction & ataxia
Ethyl Thimerosal in No evidence of damaging effects
vaccines
Organophosphate Insecticide
Organic solvents
Botulinun Toxin
Tetanus
Carbon Monoxide
Methanol Toxicity
Ethanol
Radiation
Wernickes encephalopathy & Thiamine,
Korsakoffs syndrome vitamin B1
Insecticide Miosis, blurring vision, chest tightness, wheezing, GI, Tx w/ Atropine
increased sweating, increased salivation
Workplace Organic affective syndrome: irritability, fatigability,
difficulty in concentrating, loss of interest
Mild chronic toxic encephalopathy: personality or mood
change, impairment in intellectual function
Severe chronic toxic encephalopathy: dementia with
global deterioration of memory & other cognitive functions
Clostridia Mechanism of Action Clinical Effects
Cause deficiency of Nausea, dry mouth, double
synaptic transmission; vision, weakness, difficulty
must enter axon speaking and swallowing;
terminal; prevent symmetrical flaccid paralysis
synaptic vesicles from
docking/fusing w/ presyn
term
C. tetani Tetanospasm; inactivates Lock jaw, opisthotonos
Soils and spores synaptobrevin (block
synaptic transmission
that normally inh MN
Ventilation of Form carboxyhemoglobin Headache, myalgia, dizziness,
heating sources, neuronal necrosis, and neuropsychological impairment
engine exhaust apoptosis confusion, loss of consci, death
Degeneration of retinal ganglion cells blindness
Direct effects or Effects are reversible; atrophy and loss of granule cells 1 in
2 nutritional anterior vermis
deficits Unsteady gait and nystagmus
Symptoms of intracranial mass, headaches, nausea,
vomiting, papilledema
Large areas of necrosis and adjacent edema
Wernickes Encephalopathy: ataxia, confusion, Located in
ophthalmoplegia mammillary
deficiency Korsakoffs pyschosis: severe memory defects and bodies ,
confabulation periaqueductal
Pathological changes: vascular changes, capillary tortuosity, gray
 prominence, endothelial swelling, petechial hemorrhage,
neuronal damage, macrophage response and gliosis
Alcoholic Polyneuropathy Numbness, paresthesias, weakness
Degeneration of both myelin & axons w/ axonal reaction in
anterior horn cells
Subacute combined degeneration Vitamin B12 Peripheral neuropathy, optic neuropathy; associated with
deficiency pernicious anemia
Loss of MVP, LE weakness, DTR, babinski signs;
degeneration of post/lat columns
Spongy degeneration of white matter
Kernicterus Bilirubin toxicity Hypoalbuminemia is a cause
Anoxia, acidosis
Hepatic encephalopathy Amidation of glutamateglutamine via glu synthetase takes
place in astrocytes
Brain edema, disturbances in consciousness & motor
abnormalities (pre-dominately involves glial Alzheimer type
II cells in gray matter
Inherited Nervous System Metabolic Diseases
Location Deficit Result Genetic Clinical Expression
inheritance
Neuronal Storage Diseases Gray matter Lysosomal enzyme Accumulation of Autosomal Can range from focal
(usually) enzyme substrate recessive abnormalities to mental
Leukodystrophies Myelin and white Variety of clinical Autosomal retardation
matter expression recessive
Mitochrondrial Gray matter and Oxidative Mitochondrial encephalopathy lactic
Encephalomyopathies skeletal muscle phosphorylation acidosis stroke-like episodes
Common Sphingolipidoses
Age of Enzyme Accumulated Clinical Signs Pathology
Onset Deficiency Product
Tay-Sachs Disease 3-8 mos Hexosaminidase A GM2 gangliosides Psychomotor arrest, Storage in central and
(type of Neuronal Storage exaggerated startle peripheral neurons
Disease) reflex, seizures, cherry
red spot
Metachromatic Early Cerebroside Sulfides Progressive mental and Myelin deficit in CNS/PNS,
Leukodystrophy childhood sulfatase motor deterioration, storage in glia
 peripheral neuropathy
signs
Krabbe Disease 3-6 mos Galacto- Galacto-cerebroside Mental and motor Myelin deficit; globoid
cerebrosde - deterioration, seizures, cells (large nucleated
galactosidase irritability, crying macrophages)
Degenerative Diseases
Age of Location of Clinical Features Gross/Microscopic Pathology Diagnostic
Onset Lesions Tests
Alzheimers >60 years Cortex, Memory loss, dementia Accumulation of tau, amyloid, neuritic Neuritic
Disease Early: 40- hippocampus, Gait normal, no focal weakness bodies (extracellular), neurofibrillary bodies,
60 entorhinal, or sensory loss tangles (intracellular) neurofibrillary
perirhinal Presenilin 1: chromosome 14; age 30-50 tangles
cortex, basal onset
forebrain Presenilin 2: chromosome 1; age 30-65
onset
Amyloid Precursor ptn: chrm 21; age 40-60
Apolipoptn E (e4 carriersmore amyloid
plaques)
Dementia with Elderly Subcortical Dementia plus 2 of 3: Lewy bodies with -synuclein and ubiquitin Sensitive to
Lewy Bodies areas and parkinsonism, hallucinations, or Faster progression/shorter survival anti-psychotic
(DLB) substantia fluctuating alertness/attn meds
nigra
Frontotempora Late- Frontal and Similar to Alzheimers knife-blade like atrophy of frontal and Inclusion
l Lobar middle/ temporal lobes Behavioral changes most temporal lobe bodies with
Degeneration elderly prominent , perseveration, tau fibrils in
(Picks decreased verbal fluency neurons
disease)
Huntingtons 30-50 Caudate, Behavioral, cognitive changes Gain of function of Huningtin gene CAG atrophy of
Disease years putamen, GP, and/or movement dx, esp expansion; extensive gliosis caudate
cortex chorea nucleus w/
ventricular
dilation
Wilsons 10-30 Liver, brain, Liver dysfunction Inborn error of Cu metabolism
Disease years and eye Mvmt dx (dystonia) accumulation of Cu in liver, brain, eye
(hepatolenticul Behavior/cog changes
ar
degeneration)
Amyotrophic Middle- Ventral horns, Gradual weakness w/ no Degeneration of BOTH UMN/LMN.
Lateral aged/ cortical atrophy sensory deficit Neurogenic atrophy
Sclerosis elderly in precentral
gyrus
Spinocerebella Mean age: Cerebellum Friedreich ataxia, hand Trinucleotide expansion in intron
r Ataxias 11 clumsiness, sensory deficits,
progressive deterioration
Prion diseases
Age of Location of Lesions Clinical Features Gross/Microscopic Diagnostic Tests
Onset Pathology
Creutzfeldt-Jakob 10% Polymorphism at Rapidly progressive Cortical atrophy and ventricular CSF 14,3,3
Disease (CJD) inherited codon 129 with Val; dementia and startle dilation, spongiform protein
myoclonus (some encephalitis MRI changes
ataxia)
Familial Fatal Insomnia Polymorphism at Insomnia Neuronal loss, and gliosis in specific thalamic nuclei
codon 129 with Met and inferior olivary nucleus
Variant Creutzfeldt- Cortical plaques with surrounding halo of spongiform change; mad cow disease
Jakob Disease (vCJD)
Dementia and delirium
Disease Clinical Features Diagnosis Treatment
Delirium Agitation, acute, inconsistent, fluctuating Acute onset & fluctuating course, Prevention, treat underlying illness,
alertness, hallucinations, inattention inattention, disorganized thinking, anti-psychotics, supportive care
Think: metabolic, Widespread reduction in cerebral oxidative altered LOC Contraindications: benzodiazepines,
toxic, aseptic, metabolism; failure of cholinergic sedative-hypnotic, anti-cholinergics,
increased ICP metabolism drugs of parkinsonism, narcotic
analgesics, histamine-2-receptor
blockers
Dementia Chronic, progressive, memory loss, Neuropathology: neurofibrillary
Think Alzheimers alert/attn ok, disorientation, constructional tangles/neuritic plaques in AD; lewy
or vascular apraxia bodies in PD/DLB;
dementia structural/functional imaging,
biomarkers (amyloid)
Vascular Dementia Focal motor, sensory, or reflex changes, Imaging: infarcts; ischemia Atypical Vascular Dementia:
 sudden and/or multi-stepwise decline; insidiously progressive; not
focal cognitive impairments (visuospatial stepwise showing extensive
disturbance + aphasia) confluent white matter
abnormalities on T2 and FLAIR
imaging
Normal Pressure Gait disorder, urinary incontinence, 70% respond to shunting
Hydrocephalus dementia (triad); enlarged ventricles
Dementia
associated with
Movement
Disorders
Infectious causes HIV-associated Dementia (HAD)
Can be somewhat reversible
 Local Anesthetics
Drug Ester/Amide Potency Mechanism Topical Uses Parenteral General Adverse Effects
Uses uses
Cocaine Ester- Low Blocks Laryngeal, None Topical CNS: restlessness,
metabolized voltage-gated nasal surgery, (lidocaine) dizziness, confusion,
by pl/hepatic Na channels UG circumoral paresthesis,
cholinesterase by prolonging Infiltration tinnitus, tremors,
s their seizures
Lidocaine Amide- Intermediate inactivation Dermal Epidural, Nerve block
Weak bases; state (Shingles, infiltration, & field block CV: bradycardia,
insoluble to rash), nerve block, hypotension, heart
water Cation is laryngeal, oral spinal Spinal/Epidur block, cardiac arrest
active form (prevent al anesthesia
Metabolized ventricular Peripheral
by liver P450 Non-ionized arrhythmias) neurotoxicity,
Bupivicaine High form cross None Epidural, hypersensitivity
into m. infiltration, reactions, ester
nerve block, typesPABA
spinal (sensitizing)
Mepivicaine Intermediate None Epidural,
infiltration,
nerve block,
spinal
Procaine Low None Infiltration,
(Novacain) nerve block,
spinal anes
Tetracaine
Epinephrine Adjunct for Should not be used in
local areas of end aa
vasoconstrictio (fingers, nose, penis
n; and toes) ears too
General Analgesics
Drug Mechanism of Specific Actions Potency General uses Adverse Effects
Action
Diethyl ether Correlation between Stages: Explosive, airway irritation,
 lipid I: analgesia stable CV response
solubility/potency II: delirium
Potentiate GABA III: surgical
effects; analgesia
hyperpolarization & IV: meduallary
excitability due to depression
Cl- influx and K efflux
Chloroform Arrhythmogenic, hepatotoxic,
well tolerated
Nitrous Oxide Loss of Fast induction and High MAC, not Hypnosis Autonomic
(laughing gas) consciousness & elimination metabolized Homeostasis instability
Desflurane analgesia due to Decrease vascular MAC 6 Analgesia Hypothermia
disruption of resistance, not CO Amnesia Cardiac
Enflurane neuronal firing & Decrease CO; MAC 1.7 Muscle dysrhythmias
sensory processing in produce relaxation Nausea
thalamus bronchodiliation Vomiting
Propofol Reduced motor Facilitate effects of Rapid HHAAM Hypotension, Delirium
activity due to GABA at GABA- emergence, less resp depression, 1/250000
IV inhibition of neuronal Clionophore confusion reduce cerebral estimated
firing in layer IV of compared to bld flow/ ICP ; not deaths
cerebral cortex thiopental analgesic, not
amnestic if
conscious,
antiemetic
Midazolam Facilitate effects of Less respiratory Unconsciousness
GABA depression than slower in onset,
IV Produce amnesia propofol/thiopent Ketamine: longer than
al, little effect on trauma victims, thiopental
CVS sedation of
children;
Ketamine Blocks NMDA Cause analgesia, coadmin w/ Increased HR, BP,
receptors sensory benzodiazepine ICP and
Dissociative perception, to prevent sympathetic tone
anesthesia dream- immobility and delirium and
like w/o loss of amnesia
 consciousness hallucinations
Thiopental Lower MAC Produce CNS,
IV resp, CV
depression
The Ideal Anesthetic: potent, non-irritating, noninflammable, not toxic, not metabolized, not arrythmogenic, stable cardiovascular response,
very slightly soluble in water, quite soluble in oil, unable to trigger malignant hyperthermia, stable in soda/lime, not harmful to metal fittings,
potent m relaxant
Anticonvulsants
Drug Mechanism of Metabolism Clinical Use Drug-Specific Adverse Effects Common
Action Adverse Effects
Phenytoin Na ch blockade Hepatic- P450 Partial seizures, Ataxia,nystagmus, drowsiness, lethargy, Fatigue
(Dilantin) system generalized seizures nausea, vomiting, rash, gingival Dizziness
hyperplasia, blood dyscrasias Ataxia
Carbamazepine Na ch blockade P450; induce Partial seizure; Dizziness, diplopia, nausea, ataxia, Diplopia
(Tegretol) own metab; avoid in primary blurred vision, aplastic anemia, Nystagmus
epoxidation to generalized seizures agranulocytosis, thrombocytopenia,
10,11-epoxide Stevens-Johnson syndrome
Oxcarbazepine Na ch blockade Hepatic- Seizures Dizziness, nausea, headache,
(Trileptal) induces hepatic drowsiness, ataxia, diplopia, fatigue,
enzymes and nervousness; hyponatremia
Ethosuximide Inhibits T type Absence seizures Nausea, GI, anorexia, wt loss
Cach only
Pregabalin Unknown- Renal excretion Adjunct to partial Confusion, edema, wt gain, typical side
(Lyrica) potential effect seizures effects
on -2 subunit
of Cach
Levetiracetam Unknown Renal excretion In combo with other Somnolence, fatigue, ataxia, behavioral
(Keppra) AEDs abnormalities; rare decrease in Hb&
erythrocyte count
Valproic acid Enhances GABA; Hepatic- Primarily Nausea, tremor, sedation, confusion, wt
(Depakote) modulate VG Na Glucuronidation generalized gain, hair loss, acute pancreatitis, bone
ch, inh T type st
epilepsy- 1 line mar sup, rash, hyperammonemia (fat,
Cach bald, & shaky)
Gabapentin Enhance GAD; Renal excretion, Partial seizures, Somnolence, dizziness, nystagmus,
(Neurontin) binds -2 not metabolized neuropathic pain ataxiz, fatigue, weight gain
 subunit of C ach
Lorazepam
Lamotrigine Na ch blockade Hepatic- Partial and Ataxia, dizziness, diplopia, N/V, Stevens
(Lamictal) Glucuronidation generalized seizures Johnson; 1% child/0.3% adults
Topiramate Unknown Renal and Multiple seizure Somnolence, dizziness, ataxia, difficulty
(Topamax) hepatic types w/ memory, speech/langdysfxn,
elimination diplopia, aggressive behave, anorexia,
renal lithiasis
Zonisamide Not completely Renal excretion Adjunct tx for partial Somnolence, ataxia, dizziness, fatigue,
(Zonegran) understood; T- seizures renal lithiasis, anorexia
type Ca channels,
Na channels,
carbonic
anhydrase
inhibition
Phenobarbitol
Opioid Analgesics
Drug Synthesis Types Agonistic General uses Adverse Effects Actions
Or Distribution Action Mediated by
Receptor
Subtypes
Endophins Arcuate nucleus Mu/delta Analgesia:
& ant. pit receptors mu, kappa, delta
Enkephalins Synthesized in Leu- Mu/delta Feeding:
small Met- receptors mu/kappa/delta
interneurons GI fxn: mu/kappa
Found in Sedation:
Periacqueductal mu/kappa
grey, lamina I/II Psychotomimesis:
Dynorphins Brain; often A, B, Kappa receptors Kappa
together w alpha-neo- Diuresis: kappa
enkephalins Resp fxn: mu
Morphine Papaversomnifer Pharmacokinetic Mu/kappa/delta Clinical Use: CV: myocardial O2
um s Well abs; high 1st Inhibit PAIN: post- demand, vasodilation,
pass effect; adenylcyclase operative, acute hypotension, ICP
 Contraindicatio conjugate to hyperpolarizatio MI, renal/biliary GI: constipation, biliary
ns: glucuronide in n colic pain; chronic sphincter tone/pressure,
Major: head intestines/liver pain nausea/vomiting Withdrawal
injuries, seizures, Peak effect: 1 hr GU: bladder sphincter Effects:
alcohol after inj; duration: Analgesia, tone, prolongation of Vomiting, chills,
intoxication 3-4 hrs euphoria or labor, urinary retention fever,
Relative: dysphoria, inh of Overdosestupor/coma, lacrimation,
asthma, renal cough reflex, respdep, miosis; tx w/ diarrhea,
insufficieny, miosis, physical naloxone rhinorrhea,
history of opioid dependence, resp seeking, craving
abuse, liver depression, behavior
disease sedation Occur after 8-12
*w/o loss of hrs of last dose
consciousness
Meperidine 1/10th analgesic potency of morphine; poor oral abs; Resp depression, nausea, Occur after 3 hrs
equivalent respdep; miosis (mydriasis at toxic doses); vomiting, ICP, postural last dose
high addiction liability; short duration of action; hypotension,
metabolized to normeperidinerisk of seizures constipation, urinary
Methadone Slightly more potent than morphine; less sedative Help wean off retention, itching & Onset after 24-48
&spasmogenic; effective orally heroin addict; urticarial, restlessness, hrs last dose
maintain at 40- tremulousness,
100mg hyperactivity
Fentanyl 100x more potent than morphine as analgesic; given via Patch: useful in
IV & as transdermal patch chronic pain (3
days)
Oxycodone Use in combo w/ acetaminophen (7.5mg) or aspirin (5mg)
Buprenorphi
ne
Codeine 1/10th analgesic potency of morphine; less constipation, Antitussive
lower addiction liability, less sedation/respdep; used (suppress
orally in combo w/ acetaminophen or aspirin for coughing)
moderate pain; converted to morphine by CYP 2D6
Nalbuphine Mixed opioid agonist
Parenteral (kappa)/antagonist (mu)
only
Naloxone Opioid receptor competitive Treats opioid No dependence liability;
antagonist (mu, delta, and kappa) overdose; blocks all others do; no
IV effects of constipation
morphine and
other drugs
Naltrexone Opioid antagonist, mu, delta, kappa Used to prevent Longer duration
relapse in chronic of action than
Oral alcoholics naloxone
Non-opioid Analgesic
Tramadol Synthetic codeine Weak mu agonist Mild to moderate Dry mouth, dizziness,
analog Inhibit uptake of NE and 5HT pain sedation, headache,
seizures, abuse potential-
unclear

Drugs for Parkinsons Disease

Drug Mechanism Notes Adverse Effects
Levodopa L-DOPA 100-250mg, 3-4 times Nausea, orthostatic hypotension, hallucinations, dyskinesias
(amino acid) daily Less effective with food
High dose lead to dyskinesias (peak dose chorea, biphasic chorea,
dystonia)
Carbidopa Works peripherally to block L-DOPA-DDC DA but cannot cross BBB; decrease symptoms in periphery, no CNS
effects; does not effect parkinsonism
Bromocripti For PD, DA agonist at D2 receptors
ne
Ropinirole Da agonists at D2 Longer duration of Low standing BP, nausea, dyskenisa, hallucinations, sleepiness
Pramipexol action, but not as Rare; lung & cardiac valve fibrosis, leg edema, compulsive
e effective as levodopa behaviors
Selegiline MAO-B inhibitors
Rasagiline
Entacapone COMT inhibitor used in combo therapy
Amantadin Blocks NMDA, weak inducer of DA rel; can treat dyskinesias
e
Benztropin Anticholinergics; block mAch receptor; offsets the imbalance between Ach and DA
e
Apomorphi DA agonist at D1 and D2 receptors
ne
Drugs for Multiple Sclerosis
Drug Type of Drug Mechanism of Action Adverse Effects
Interferone-beta Ag non-selective immunomodulators, proposed to act through inhibiting IFN-gamma activity
Glatiramer Ag selective
acetate
Natalizumab Humanized Reduce the ability of immune cells to Progressive multifocal
monoclonal Ab cross BBB leukoencephalopathy
IV against cell
adhesion molecule
alpha4-integrin
Antithrombotic agents
Clopidogrel Pro-drug, function Irreversible inhibits P2Y12 receptor Hemorrhage, neutropenia
related to ADP which is important in platelet
receptor on platelet aggregation and cross-linking of fibrin
cell membrane by blocking the activation of
P2Y12 glycoprotein IIa/IIIb pathway;
metabolized by CYP2C19
Aspirin Irreversibly inhibits COX 1 GI ulcers, stomach bleeding, tinnitus
Drugs for Dementia
Donepezil Cholinesterase Slows the breakdown of Ach by blocking Nausea, vomiting, loss of appetite,
Galantamine inhibitors acetylcholinesterase levels of Ach increased frequency of bowel
Rivastigmine increase movements/diarrhea
Memantine NMDA antagonist No evidence it can prevent or slow neurodegeneration
Drugs for Migraine
Sumatriptan Abortive for cluster 5HT agonist; exerted in bile and urine
and migraine 4-6mg sc at onset for cluster H/A, poor bioavailability with oral administration,
faster acting, but with shorter duration with injection
Dihydroergotam Abortive for cluster Act on 5HT receptors (agonistic) May increase BP, coronary artery
ine and migraine vasoconstriction; inhibition of pro- vasopasm, MI, ventricular fibrillation
inflammatory neuropeptide release
Propanolol Prophylactic for Decrease frequency and severity of Drowsiness, difficulty breathing, slow
migraine, -adr migraines heartbeat, cold hands/feet, depression
blocker
Valproic acid Prophylactic for migraine, and cluster H/A, anti-convultant
Amitryptyline Prophylactic for migraine, tricyclic anti-depressant-inhibits Causes delirium
5HT/NE uptake
Topiramate Prophylactic for migraine and cluster, anti-convulsant
Know that the following classes of drugs can cause Delirium
Anticholinergics, Opioids, Benzodiazepines, narcotic analgesics, sedative-hypnotic, histamine 2-receptor blockers