Anatomy 27, Eye Infections

1. Microbial Agents, Host Risk Factors, and Treatment – Conjunctivitis

Type Common Agents Risk Factors Treatment

Adenovirus (most common), Supportive care, HSV → Acyclovir

Viral URTI, poor hygiene
HSV (blindness), Enteroviruses + Famciclovir

Bacterial H. influenzae, S. pneumoniae, Topical antibiotics (e.g.,

Children, contact lens wearers
(unilateral) S. aureus erythromycin); systemic if severe

Contact Extended lens wear, Fluoroquinolone eye drops; urgent

Pseudomonas aeruginosa
lens contaminated solutions ophthalmology referral

Gonorrhea: erythromycin +
Neonatal N. gonorrhoeae, C. Vaginal birth from infected
3rd-gen cephalosporin;
/sexual trachomatis mother
Chlamydia: oral azithro

Allergic Not infectious Atopy, environmental allergens Antihistamines, lubricants

2. Describe the physiological properties and clinical significances of Chlamydia spp.

●​ Obligate intracellular Gram-negative bacteria that lack a classic peptidoglycan wall,
making them resistant to β-lactam antibiotics. They exist in two forms:
○​ Elementary body: extracellular, infectious, metabolically inactive.
○​ Reticulate body: intracellular, replicative, metabolically active.
●​ Organism replicates inside epithelial cells, forming inclusion bodies (diagnostic).
●​ Chlamydia trachomatis: causes trachoma- insects and fomites (serovars A–C) and
inclusion conjunctivitis- STI (serovars D–K).
●​ leading cause of irreversible infectious blindness globally and also causes neonatal
and adult conjunctivitis, often as an STI or via vertical transmission during birth.
●​ Diagnostic methods include NAAT and Giemsa stain for intracellular inclusions.
●​ Treated with azithromycin or doxycycline (adults); erythromycin in neonates.

3. Parasitic etiologies, their epidemiology, and clinical manifestation of eye infections

●​ Acanthamoeba spp.:
○​ Found in water (tap, pools, lakes) and soil.
○​ Associated with contact lens wear, poor hygiene or contaminated solutions.
○​ Causes Acanthamoeba keratitis: painful, progressive infection → blindness.
○​ Diagnosis: corneal scrapings; treatment complex, typically requires a specialist.
●​ Onchocerca volvulus:
○​ Transmitted by blackflies (Simulium spp.) in Africa and Central America.
○​ Causes onchocerciasis (irreversible river blindness), resulting from chronic
inflammatory damage to ocular tissues due to microfilariae.
●​ Loa loa (African eye worm):
○​ Transmitted by adult deer flies (Chrysops spp.). Endemic in West Africa.
○​ Causes transient conjunctivitis and Calabar swellings (egg-sized lesion or
swollen extremities), but generally does not impair vision.
4. Adenovirus & Pseudomonas aeruginosa – Physiology, Virulence, Clinical Significance
Adenovirus
●​ Structure: Non-enveloped, dsDNA virus
●​ Virulence Factors: Fiber proteins (attach to host cells), resistance to drying
●​ Clinical Significance: Most common cause of viral conjunctivitis (types 8, 19)
○​ Often follows URTIs; Epidemic keratoconjunctivitis in outbreaks
○​ Supportive treatment only
Pseudomonas aeruginosa
●​ Structure: Aerobic Gram-negative rod, oxidase-positive
●​ Virulence Factors: Exotoxins, biofilm formation, elastase, pili
○​ Grows in moist environments (e.g., contact solutions)
●​ Clinical Significance:
○​ Common in contact lens–related keratitis and otitis externa
○​ Can cause rapidly progressive corneal ulcers → blindness
●​ Treatment:
○​ Topical fluoroquinolones (e.g., ciprofloxacin)
○​ Urgent ophthalmology referral for keratitis

Summary
1. Key eyelid infection agents?
●​ Staphylococcus aureus – Gram-positive cocci in clusters
●​ Streptococcus pneumoniae – Gram-positive lancet-shaped diplococci
●​ Haemophilus influenzae – Gram-negative coccobacilli
commonly cause blepharitis, hordeolum (stye), or other eyelid margin infections.
2. Key viral conjunctivitis agents?
●​ Adenovirus – Non-enveloped, double-stranded DNA virus
●​ Herpes simplex virus (HSV) – Enveloped, double-stranded DNA virus
○​ HSV can cause dendritic corneal ulcers and recurrent infections.
●​ Enteroviruses – Non-enveloped, positive-sense single-stranded RNA viruses
●​ Varicella-zoster virus (VZV) – Enveloped, double-stranded DNA virus
3. Contact lens-wear-related conjunctivitis agents?
●​ Pseudomonas aeruginosa – Gram-negative rod
○​ rapid, destructive keratitis and corneal ulcers(extended-wear contact lens users)
●​ Acanthamoeba – Amoebic protozoan, not visible on Gram stain
○​ Acanthamoeba keratitis, poor lens hygiene/contaminated water exposure
4. Neonatal acute conjunctivitis: prevention?
●​ Neisseria gonorrhoeae – Gram-negative diplococci (glucose positive only)
○​ Prevention: topical erythromycin ointment; Treatment: systemic ceftriaxone
●​ Chlamydia trachomatis – Obligate intracellular, Gram-negative-like (no typical
peptidoglycan; shows inclusion bodies)
○​ Prevention: maternal screening/treatment; Treatment: erythromycin, neonates
5. Africa, Central America – eye worms? Onchocerca volvulus (causes river blindness)
○​ Transmitted by blackflies (Simulium). Not seen on Gram stain
6. Eye worms? Loa loa
 ●​ Transmitted by Chrysops (deer flies); Seen as moving adult worms under conjunctiva;
not Gram-stainable, Causes transient conjunctivitis, not vision-threatening
7. Amebic encephalitis, entering through the nose? Naegleria fowleri
●​ Free-living amoeba, trophozoite form seen on wet mount or H&E stain, not Gram stain
Question Pathogen(s) Gram Stain / Type Clinical Notes

Key eyelid infection Staphylococcus Gram-positive cocci in

Blepharitis, stye (hordeolum)
agents aureus clusters

Streptococcus Gram-positive Can cause eyelid and conjunctival

pneumoniae lancet-shaped diplococci infections

Haemophilus Gram-negative
Common in children
influenzae coccobacilli

Key viral conjunctivitis Non-enveloped dsDNA

Adenovirus Most common cause; post-URTI
agents virus

Herpes simplex virus

Enveloped dsDNA virus Dendritic ulcers; risk of blindness
(HSV)

Non-enveloped ssRNA
Enteroviruses May co-occur with VZV in children
virus

Varicella-zoster virus
Enveloped dsDNA virus Vesicular eyelid lesions
(VZV)

Contact Rapidly causes corneal ulcers,

Pseudomonas
lens-wear-related Gram-negative rod especially with extended-wear
aeruginosa
conjunctivitis lenses

Protozoan (not visible Causes Acanthamoeba keratitis;

Acanthamoeba spp.
on Gram stain) poor lens hygiene risk

Neonatal acute Gram-negative Prevent with erythromycin

Neisseria
conjunctivitis – diplococci ointment; treat with systemic
gonorrhoeae
prevention (glucose-only oxidizer) ceftriaxone

Chlamydia Obligate intracellular, Inclusion conjunctivitis; treat with

trachomatis Gram-negative-like oral erythromycin

Africa, Central America – Filarial nematode (not River blindness; blackfly

Onchocerca volvulus
eye worms Gram-stainable) transmission

Filarial nematode (not Transient conjunctivitis; deer fly

Eye worms Loa loa
Gram-stainable) vector

Amoeba (trophozoites
Amebic encephalitis (via Enters via olfactory nerve; causes
Naegleria fowleri seen on wet mount or
nose) fatal PAM
H&E)
Read summary slide from Lippincott
Summary Slides to Follow
 Anatomy 28, ENT Infections
1. Common pathogens and host risk factors associated with otitis externa and acute otitis media
●​ Otitis externa (Swimmer’s Ear):
○​ Pseudomonas aeruginosa (most common, moisture-exposed ear canals)
○​ Staphylococcus aureus
○​ Aspergillus species (occasional)
○​ Risk factors: moisture, trauma (e.g., cotton swabs), immunocompromised (e.g.,
diabetes — risk for malignant otitis externa)
●​ Acute otitis media: secondary infections — TQ, know classifications
○​ Streptococcus pneumoniae, gram (+) cocci (non-vaccinated strains)
○​ Haemophilus influenzae, gram (-) cocci (nontypeable strains)
○​ Moraxella catarrhalis, gram (-) rods
○​ Risk factors: age 6–36 months, recent viral URTI, cleft palate,
immunodeficiency, enlarged adenoids, exposure to tobacco smoke

2. Physiological properties, clinical significance, and treatment of Moraxella catarrhalis

●​ Physiology: Gram-negative diplococcus, strict aerobe, oxidase positive, does NOT
ferment carbohydrates (differentiates from Neisserias)
●​ Produces β-lactamases → resistant to ampicillin/amoxicillin alone
●​ Significance: otitis media and sinusitis in children, COPD exacerbations in adults

3. Common bacterial and fungal etiologies of sinusitis

●​ Bacterial:
○​ Streptococcus pneumoniae (+ cocci) Haemophilus influenzae (- rods),
Moraxella catarrhalis (- rods)
●​ Fungal:
○​ Aspergillus species — common in both immunocompetent and
immunocompromised
○​ Mucorales (e.g., Rhizopus) — particularly in diabetic ketoacidosis or
immunosuppression – most dangerous

4. Classification, physiology, clinical manifestations, diagnosis, tx of Aspergillus and Mucorales

●​ Aspergillus: Septate hyphae with v-shaped branch. Mold with green spores.
Ubiquitous in air/soil. Not dimorphic
○​ Causes allergic sinusitis, fungal ball (mycetoma), invasive disease in
neutropenia
●​ Mucorales (e.g., Rhizopus): Broad, right angle branching, aseptate hyphae, mold with
black spores
○​ Causes rhinocerebral mucormycosis (necrotic lesions) in DKA or
hematologic malignancy
○​ Diagnosis: biopsy (histopathology best), culture may be negative
○​ Treatment: IV amphotericin B + surgical debridement
5. Common infectious causes of sore throat/rhinorrhea and host factors
●​ Viral (most common overall):
○​ Rhinovirus, Adenovirus, Enteroviruses, HSV, Influenza, Parainfluenza
○​ Common in healthy children and adults
●​ Bacterial:
○​ S. pyogenes (Group A Strep) — most common bacterial cause in children
○​ Neisseria gonorrhoeae — consider in sexually active teens
○​ Haemophilus influenzae (capsular type B) — epiglottitis in unvaccinated kids
■​ EMERGENCY
○​ Corynebacterium diphtheriae — pseudomembrane formation in unvaccinated
○​ Mycoplasma pneumoniae, Chlamydophila pneumoniae — atypical pneumonia

6. Physiology, clinical manifestations, and management of Candida spp.

●​ Physiology: Yeast; part of normal flora (skin, GI, vagina)
○​ C. albicans forms pseudohyphae and is germ tube positive
○​ Common nosocomial pathogen, especially in immunosuppressed
●​ Clinical manifestations:
○​ Oral thrush, esophagitis, diaper rash (satellite lesions), vaginal candidiasis,
catheter-related infections
●​ Treatment:
○​ Superficial: topical nystatin
○​ Systemic: oral fluconazole
○​ Invasive: IV amphotericin B or echinocandins
 Neuro 57, Degenerative Motor Systems Neuropathology
1. Pathogenesis of Parkinson’s Disease and “Atypical” Parkinsonism
Parkinson’s Disease (PD): Loss of dopaminergic neurons in the substantia nigra pars
compacta, leading to decreased stimulation of the motor cortex, thus suppressing movement
●​ Parkinsonism: clinical syndrome with tremor, rigidity, bradykinesia, and instability
●​ Parkinson’s disease-associated dementia: cognitive and motor symptom onset
are >1 year apart
●​ Dementia with Lewy bodies: onset of cognitive and motor symptoms <1 yr apart
Pathology: Pallor of substantia nigra, Lewy bodies (α-synuclein inclusions), neuronal loss
Pathogenesis:
●​ α-synuclein accumulation and aggregation
●​ Mitochondrial and lysosomal dysfunction
●​ Inflammatory responses, possibly triggered in the gut
Course: Men > women. Progressive, often over 10–15 years; dementia develops in ~20%
Death: Often due to aspiration pneumonia or falls
Atypical Parkinsonian Syndromes: features of parkinsonism but minimally responsive to
L-DOPA
●​ Progressive Supranuclear Palsy (PSP): Early falls, truncal rigidity, eye movement
abnormalities, pseudobulbar palsy. Tau-positive inclusions in neurons and glia
●​ Corticobasal Degeneration: Asymmetric motor symptoms (limb jerking), apraxia. Tau
pathology in cerebral cortex
●​ Multiple System Atrophy (MSA): Parkinsonism, cerebellar signs, autonomic failure
(orthostatic hypotension), α-synuclein in oligodendrocytes (not neurons), Cognition is
typically spared

2. Genetics of Huntington's Disease

●​ Inheritance: Autosomal dominant, complete penetrance at ≥40 CAG repeats
●​ Gene: HTT gene encoding huntingtin protein
●​ Pathogenesis: Expansion of CAG repeats leads to polyglutamine tract in huntingtin
●​ Symptoms: Chorea (writhing movements), Cognitive/psychiatric decline
○​ Onset typically in 30s–50s; death in ~15 years (often from pneumonia or suicide)
●​ Pathology: Atrophy of caudate and putamen, Dilated ventricles, Inclusions containing
ubiquitinated huntingtin; Length of repeat correlates with age of onset but not
severity of initial symptoms or course of illness

3. Friedreich’s Ataxia and Spinocerebellar Ataxias (SCAs)

Friedreich’s Ataxia
●​ Inheritance: Autosomal recessive (most common AR ataxia)
●​ Gene: GAA repeat expansion in frataxin, a mitochondrial protein
●​ Pathogenesis: Impaired iron regulation → mitochondrial dysfunction → oxidative stress
●​ Clinical:
○​ Mixed motor, sensory, and cerebellar deficits
○​ Hypertrophic cardiomyopathy, scoliosis
○​ Onset ~10–15 years, wheelchair-bound by 30s, average death ~38
SCAs
●​ Inheritance: Autosomal dominant
●​ Pathology: Degeneration of cerebellum, white matter tracts, spinal cord
●​ Features: Cerebellar and sensory ataxia, spasticity, peripheral neuropathy
○​ Some forms: CAG repeat expansions with polyglutamine inclusions
○​ Cognitive impairment may occur

4. ALS: Clinical Features, Pathogenesis, and Morphology

●​ Amyotrophic Lateral Sclerosis (ALS):
○​ Mixed UMN and LMN signs:
■​ UMN: spasticity, clonus, pseudobulbar palsy
■​ LMN: atrophy, fasciculations, bulbar palsy
○​ No sensory or sphincter deficits
●​ Pathogenesis: Mostly sporadic; ~10% familial (AD), Linked to RNA-binding proteins and
glutamate excitotoxicity
●​ Morphology: Atrophic anterior spinal roots, Loss of motor neurons, gliosis, degeneration
of corticospinal tracts
●​ Prognosis: Median survival ~5 years; death from respiratory failure or aspiration
pneumonia

5. Acquired Metabolic and Toxic CNS Diseases

Wilson’s Disease
●​ AR defect in copper metabolism → basal ganglia dysfunction
●​ Neurologic: tremor, rigidity, ataxia
●​ Psychiatric symptoms: affective and cognitive changes
Vitamin Deficiencies
●​ Thiamine (B1):
○​ Wernicke encephalopathy: ophthalmoplegia, ataxia, confusion
○​ Korsakoff syndrome: amnesia, confabulation
●​ Vitamin B12:
○​ Subacute combined degeneration of spinal cord (posterior + corticospinal
tracts)
○​ Paresthesias, gait ataxia, possible irreversible paraplegia
Other Toxins
●​ Synthetic heroin, pesticides → Parkinsonian symptoms
●​ Alcohol, chemotherapy → cerebellar atrophy and peripheral neuropathy
 Neuro 58, Final Degenerative Cognitive Neuropathology
1. Basic Epidemiology & Pathophysiology of Alzheimer’s Disease (AD)
●​ Most common cause of dementia in the elderly.
●​ Abnormal cleavage of amyloid precursor protein (APP) by β- and γ-secretase produces
aggregate Aβ peptides in neuropil that form neuritic plaques.
●​ Hyperphosphorylated tau aggregates into neurofibrillary tangles.
●​ Neuritic plaques and neurofibrillary tangles BOTH must be seen
○​ Neurofibrillary tangle burden correlates better with cognitive decline than plaque.
○​ Mutations of tau cause FTLD without amyloid peptide accumulation
●​ Genetics:
○​ Familial early-onset forms: mutations in APP, PSEN1, PSEN2.
○​ Risk factor for late-onset: ApoE ε4 allele (dose-dependent risk).

2. Lewy Body Disease

●​ Definition: Spectrum of disease with α-synuclein-containing Lewy bodies, including
Parkinson’s disease and dementia with Lewy bodies.
●​ Lewy Bodies: Found in substantia nigra, entorhinal cortex; composed of α-synuclein.
●​ Clinical Spectrum:
○​ Parkinson’s disease: motor symptoms precede cognitive by >1 year.
○​ Dementia with Lewy bodies: Cognitive + motor symptoms <1 year apart.
■​ Visual hallucinations (often of children/small animals).
■​ Fluctuating attention and alertness.
■​ Parkinsonian motor features.
■​ Preserved cingulate cortex metabolism on PET (cingulate island
sign).

3. Assessment of Cerebrovascular Disease at Autopsy

●​ Common findings: Ischemic white matter changes, lacunar infarcts, microinfarcts,
macroinfarcts, CAA, arteriolosclerosis.
○​ Found in isolation or as co-pathology in AD or Lewy body disease.
●​ Autopsy techniques:
○​ Gross exam: look for infarcts, hemorrhages.
○​ Histology: assess white matter rarefaction, perivascular spaces, vessel wall
changes (hyalinization, necrosis), microinfarcts.
○​ Immunohistochemistry: Aβ staining in vessels for CAA.
●​ Clinical correlation:
○​ Stepwise cognitive decline and late-onset memory issues suggest vascular
dementia.
○​ Strategic infarcts (e.g., hippocampus) may cause disproportionate cognitive
impact.
4. Frontotemporal Lobar Degenerations (FTLDs)
●​ Heterogeneous group causing focal degeneration of frontal and/or temporal lobes.
●​ Clinical presentations:
○​ Behavior variant FTD (bvFTD)
○​ Semantic dementia
○​ Progressive non-fluent aphasia
●​ Pathological subtypes:
○​ FTLD-tau: Includes Pick’s disease (Pick bodies), PSP, corticobasal
degeneration.
○​ FTLD-TDP: TDP-43-positive cytoplasmic inclusions; includes cases with
progranulin mutations.
●​ Onset: Earlier than AD; accounts for 12–20% of dementias.

5. Rapidly Progressive Dementias and Prion Disorders

●​ Prion diseases:
○​ Include Creutzfeldt-Jakob disease (CJD), variant CJD, fatal familial insomnia,
Gerstmann-Sträussler-Scheinker disease.
○​ Can be sporadic, inherited, or acquired.
●​ Pathogenesis:
○​ Normal prion protein (PrPc) converts to PrPsc (β-sheet conformation) →
aggregation and neurotoxicity.
○​ PrPsc is resistant to protease degradation and can induce further misfolding.
●​ Clinical features:
○​ Rapid cognitive decline (<2 years).
○​ Myoclonus, ataxia, visual changes, REM sleep disturbances.
○​ MRI: cortical ribboning and striatum hyperintensity on DWI.
●​ Pathology:
○​ Spongiform change (vacuolization) in cortex.
○​ Minimal to mild gross atrophy unless long duration.
 Neuro 59, Cerebrum Clinical Examination
1. Arteries in the “Vascular Supply of Brain Structures” Section – DRAW THIS OUT
Circle of Willis: connects ICA and vertebral-basilar systems
●​ Internal carotid artery (ICA) gives rise to:
○​ Ophthalmic a. → central retinal a.
○​ Anterior cerebral a. (ACA)
○​ Middle cerebral a. (MCA)
○​ Anterior choroidal a. (AChA)
○​ Posterior communicating a.
●​ Vertebral-basilar system gives rise to:
○​ Posterior cerebral a. (PCA)
○​ Superior cerebellar a.
○​ Basilar a.

2. Branching Pattern of Cerebral Arteries and Functional Associations

ACA: Supplies medial frontal/parietal lobes (e.g., lower extremity M1/S1).
●​ Deep branch: medial striate a. → anterior internal capsule, caudate.
MCA:
●​ Superior division → lateral frontal/parietal cortex (face/arm M1/S1, Broca's).
●​ Inferior division → lateral temporal/parietal cortex (Wernicke’s, visual fields).
●​ Deep branches (lateral striate aa.) → putamen, globus pallidus externus, PLIC (dorsal),
corona radiata, arcuate fasciculus
PCA: Supplies occipital lobe (primary visual cortex), inferior temporal lobe.
●​ Deep branches (e.g., thalamoperforating aa.) → thalamus.
AChA: Supplies optic tract, LGN, PLIC (ventral), choroid plexus, hippocampus, basal ganglia.

3. Territorial Stroke Syndromes (Major Arteries)

Artery Key Findings

ACA Contralateral LE motor/sensory loss

MCA, Superior Contralateral face/UE weakness ± sensory loss, Broca’s aphasia (dominant) or motor
Division aprosodia (non-dominant)

MCA, Inferior Contralateral sensory loss (face/arm), Wernicke’s aphasia (dominant), neglect
Division (non-dominant), contralateral visual field loss

Pure motor contralateral hemiparesis (face/body), ± aphasia (dominant) or neglect

MCA, Deep
(non-dominant)

Global aphasia (dominant), contralateral: hemiplegia, hemianesthesia, hemianopia,

MCA, Stem
ipsilateral gaze preference, profound left hemineglect

PCA Contralateral hemianopia with macular sparing, alexia without agraphia (dominant)

ACA-MCA
“Man in the barrel” syndrome: bilateral proximal UE/LE weakness, transcortical aphasias
Watershed
4. Lacunar Syndromes (Deep Small-Vessel Strokes)
Syndrome Vascular Territory Clinical Features

Pure motor Posterior limb of internal capsule (AChA or Contralateral face/body

hemiparesis MCA deep) or ventral pons (basilar branches) weakness ± dysarthria

Thalamus (PCA –
Contralateral hemisensory
inferolateral/thalamogeniculate branches
Pure sensory stroke loss, may develop thalamic
supplying the ventral posterior nuclei- medial
pain syndrome
and lateral)

Dysarthria–clumsy Dysarthria, clumsy hand,

Basis pontis (lacune)
hand syndrome mild hemiparesis

Weakness + ataxia on the

Ataxic hemiparesis Internal capsule, pons, or corona radiata
same side
 Neuro 60, Atypical Infectious Encephalopathies I
Four Most Common Opportunistic Fungal Pathogens of the CNS
Key
Fungus Form in Tissue Clinical Manifestations Diagnosis
Features

Yeast + Thrush, vaginitis, Gram stain, KOH,

Candida Germ tube +
pseudohyphae endocarditis (IVDU) culture

Yeast with Meningitis (especially in India ink,

Cryptococcus LARGE Urease + HIV+), pneumonia, mucicarmine stain,
capsule disseminated infection Ag test, culture

45° Fungal balls in lungs, Culture with green

Aspergillus Septate mold
branches sinusitis, catheter infections spores, histology

Nonseptate 90° Rhinocerebral infection in

Mucor/Rhizopus KOH prep, culture
mold branches DKA

Typical CSF Profile in Fungal and Mycobacterial CNS Infections

Parameter Fungal/Mycobacterial Infection

Opening Pressure Normal or mildly increased

WBC Count 5–2000 (lymphocyte-predominant)

Glucose Low (≤45 mg/dL)

Protein High (>60 mg/dL)

Cryptococcus spp.
●​ C. neoformans: affects immunocompromised (HIV+); soil w/ bird droppings
●​ C. gattii: healthy and immunocompromised; eucalyptus and other trees
●​ Transmission: Inhalation of spores (no human-to-human spread)
●​ Inhaled → enters lungs → transforms to yeast form → travels hematogenously to CNS
●​ Properties: Yeast form only (monomorphic) with LARGE, thick capsule
●​ Clinical Manifestations: Meningitis (esp. in HIV+ patients)
●​ Diagnosis: India ink or mucicarmine stain (red capsule); mucoid, urease + colonies
●​ Treatment:
○​ Asymptomatic/mild: fluconazole
○​ Severe/CNS: amphotericin B + flucytosine → fluconazole maintenance
○​ Prophylaxis: fluconazole if CD4 <100 + cryptococcal Ag+

Taenia solium & Neurocysticercosis

●​ Taeniasis: Ingest cysticerci (undercooked pork) → GI infection (egg/proglottids in
stool);
●​ Neurocysticercosis (only from T. solium and requires ingestions of EGGs):
○​ Ingestion of eggs → larvae migrate to brain (common parasitic CNS infection)
○​ Symptoms: new-onset seizures, headaches, N/V (caused by inflammation)
 ●​ Diagnosis:
○​ CT/MRI: cysts
○​ Serology: anti-Taenia antibodies
○​ Stool: proglottids (for intestinal form)
●​ Treatment:
○​ Albendazole or praziquantel, Steroids (reduce inflammation), Anti-epileptics
○​ Surgery (select cases)

8. Naegleria fowleri
●​ Transmission:
○​ Warm freshwater entry via nasal mucosa during swimming
○​ Trophozoites migrate along olfactory nerve to CNS
●​ Pathogenesis: Rapid invasion → inflammation → necrosis (highly fatal)
●​ Clinical: Primary amebic meningoencephalitis (PAM): SEVERE AND SUDDEN
○​ Stage 1: severe frontal headache, high fever, anosmia
○​ Stage 2: seizures, hallucinations, coma
○​ Almost uniformly fatal
●​ Diagnosis:
○​ CSF: trophozoites (infective stage and main diagnostic form)
○​ PCR, antigen, biopsy
○​ Contact CDC for assistance
●​ Treatment:
○​ Amphotericin B, miltefosine, azithromycin, rifampin, fluconazole, steroids
○​ Hypothermia
●​ Prevention: Avoid warm freshwater; use sterilized water for nasal rinses

9. Toxoplasmosis
●​ Transmission:
○​ Undercooked meat with tissue cysts
○​ Cat feces with oocysts
●​ Pathogenesis:
○​ Cysts → bradyzoites → convert to invasive trophozoites in
immunocompromised
●​ Clinical:
○​ Immunocompetent: mononucleosis-like
○​ Immunocompromised: encephalitis, ring-enhancing lesions
○​ Congenital: chorioretinitis, hydrocephalus, intracranial calcifications
●​ Diagnosis:
○​ Serology (IgM, IgG)
○​ Imaging: MRI (ring-enhancing lesions)
○​ PCR or histology (tachyzoites)
●​ Treatment: Pyrimethamine-sulfadiazine + leucovorin
○​ Corticosteroids (if cerebral edema)
 Neuro 61, Atypical Infectious Encephalopathies II
1. Properties of prions and structural vs functional significances of PrPc and PrPSc
●​ Prions are infectious misfolded proteins (PrPSc) that convert normal cellular prion
proteins (PrPC) into more PrPSc, leading to neurodegeneration.
●​ PrPC (normal):
○​ Structure: rich in α-helices, monomeric
○​ Function: Cu-binding, interacts with NMDA/K+ channels, \ role in memory
○​ Location: plasma membrane; Turnover: hours; Protease-sensitive
●​ PrPSc (abnormal):
○​ Structure: rich in β-pleated sheets, multimeric
○​ Function: no known physiological function; causes neurotoxicity
○​ Location: cytoplasmic vesicles and secreted
○​ Turnover: days; Protease-resistant; Aggregates into amyloid plaques

2. Pathological findings, clinical manifestation, and epidemiology of human prion diseases

Form Etiology Clinical Features Pathology

Spongiform vacuoles,
Sporadic Spontaneous Rapid dementia, myoclonus
amyloid plaques, no
CJD mutation or conversion (>90%), death <6 mo
inflammation

Earlier onset, insomnia

Genetic (e.g., PRNP autosomal Similar spongiform and
(FFI), cerebellar symptoms
FFI, GSS) dominant mutations amyloid pathology
(GSS)

Psychiatric symptoms,
BSE-like prion (from Amyloid plaques, young
Variant CJD sensory changes,
cattle) onset (~26 yrs)
cerebellar signs

Contaminated
Depends on route; long
Iatrogenic instruments, HGH, Same spongiform changes
incubation (4–40 years)
grafts

Cerebellar ataxia, tremors,

Kuru Ritualistic cannibalism Same spongiform changes
emotional lability

3. Sporadic vs variant Creutzfeldt-Jakob diseases for diagnosis and clinical progression

●​ Sporadic CJD
○​ Age: 45–75 yrs (peak 60–65)
○​ Rapid progression (~6 months)
○​ Symptoms: dementia, myoclonus (startled-induced), ataxia
○​ No clear exposure risk
●​ Variant CJD
○​ Age: ~26 years
○​ Slower progression (~14 months)
○​ Symptoms: behavioral changes early, followed by sensory and movement issues
○​ Linked to BSE-contaminated meat
●​ Diagnosis: clinical diagnosis, elevated 14-3-3 protein in CSF, RTQuIC
4. Pathogenesis and clinical manifestations of HIV-associated neurocognitive disorders
●​ Pathogenesis:
○​ HIV infects brain macrophages and microglia → chronic inflammation and
neuronal loss
○​ Causes cerebral atrophy (especially frontal and temporal lobes)
●​ Clinical Manifestations:
○​ Early: difficulty concentrating, depression, apathy
○​ Later: dementia, memory loss (judgment often intact)
●​ ART (antiretroviral therapy):
○​ Suppresses CNS viral load
○​ Reduces prevalence/severity of neurocognitive symptoms

5. Review the biology of Treponema pallidum

●​ Spirochete: corkscrew-shaped, motile
●​ Cannot be cultured (fastidious); Specific Treponemal Antibody Detection for
neurosyphilis
●​ Sensitive to drying, heat (>42°C), disinfectants
●​ Virulence factors:
○​ Outer membrane proteins (adhesion)
○​ Hyaluronidase (tissue infiltration)
○​ Fibronectin coat (antiphagocytic)
●​ Transmission: sexual, congenital
●​ Treated with penicillin

6. Describe the clinical manifestations of primary, secondary, and tertiary syphilis

●​ Primary: painless chancre at site of infection; heals in 3–6 weeks
●​ Secondary: systemic symptoms, including rash (palms/soles), lymphadenopathy,
mucous patches
●​ Tertiary: gummatous lesions, cardiovascular syphilis, neurosyphilis

7. Explain the pathogenesis and key symptoms of early and late neurosyphilis
●​ Early Neurosyphilis (CSF, meninges, vessels):
○​ Asymptomatic: positive CSF VDRL
○​ Symptomatic meningitis: headache, confusion, stiff neck, hydrocephalus
○​ Ocular/Otosyphilis: visual or hearing loss
●​ Late Neurosyphilis (brain/spinal cord parenchyma):
○​ General paresis: progressive dementia, psychosis
○​ Tabes dorsalis: locomotor ataxia, sensory ataxia, lightning pains, Argyll
Robertson pupils (pupils constrict w/accommodation but not light)
 Neuro 62-63, Applying the Neurologic Exam I-II
1. Utilize the Neurologic Exam to Localize Lesions
●​ Left/Dominant Hemisphere: Aphasias (Broca’s, Wernicke’s), Apraxia, acalculia
●​ Right/Non-Dominant Hemisphere: Hemi-neglect, anosognosia
Localization by Structure
Region Key Signs

Frontal Cortex (M1, SMA) UMN weakness, frontal release signs

Parietal Cortex Sensory loss, neglect (non-dominant), cortical sensory deficits

Thalamus Profound contralateral sensory loss, thalamic pain

Internal Capsule Pure motor hemiparesis, contralateral face + arm + leg weakness

Brainstem (medial vs Alternating syndromes with crossed findings: ipsilateral CN +

lateral) contralateral body signs

Cerebellum Ipsilateral ataxia, intention tremor

Spinal Cord Sensory level, UMN signs below, LMN at level, dissociated loss

2. Recognize Highlighted Brainstem Syndromes and Their Etiologies

Syndrome Artery Key Findings

Vertebral or Contralateral hemiparesis (CST), contralateral

Medial
Anterior spinal hemianesthesia, body, NOT face (ML), ipsilateral tongue
Medullary
artery paralysis (CN XII)

Ipsilateral face pain/temp loss (CN V), contralateral body

Lateral
Vertebral artery pain/temp loss (STT), ipsilateral Horner's, dysphagia (CN
Medullary
IX/X), ataxia

Contralateral hemiparesis (CST), ipsilateral lateral rectus palsy

Medial Pontine Basilar artery
(CN VI nucleus), ± facial weakness

Ipsilateral facial weakness (CN VII), vertigo, ataxia, hearing

Lateral Pontine AICA (± SCA)
loss, Horner’s, contralateral body pain/temp loss (STT)

Locked-In Bilateral ventral Quadriplegia, preserved vertical eye movements, full

Syndrome pons (basilar) awareness and comprehension.
3. Recognize Highlighted Spinal Cord Syndromes and Their Etiologies
Syndrome Etiology Key Findings

Ipsilateral UMN signs and

Brown-Séquard vibration/proprioception loss; contralateral
Trauma, MS, tumor
(Hemicord) pain/temp loss
Dissociated sensory loss

"Cape-like" bilateral pain/temp loss,

Central Cord Syndrome Syrinx, trauma
possible arm > leg weakness

Bilateral pain/temp loss, UMN signs, bladder

Anterior Cord Anterior spinal artery
dysfunction; dorsal column spared
Syndrome infarct, trauma
lower spinal cord

Subacute Combined Bilateral UMN signs, sensory ataxia, loss of

B12 deficiency
Degeneration vibration/proprioception

Cauda Equina Disc herniation, tumor, Saddle anesthesia, LMN signs,

Syndrome trauma bladder/bowel/sexual dysfunction

Degeneration of UMN Mixed spastic + flaccid paralysis, no sensory

ALS
+ LMN loss

Poliovirus (ventral horn

Poliomyelitis Asymmetric flaccid paralysis, no sensory loss
LMNs)
 Neuro 64, Headache
Common Primary Headache Syndromes
Cluster Headache Paroxysmal
Feature Migraine with Aura Tension-Type
(TAC) Hemicrania (TAC)

Unilateral (70%); Always unilateral

Location Bilateral Strictly unilateral (>95%)
Bifrontal/global (30%) (orbital/temporal)

Gradual; “dull”,
Abrupt; deep, Abrupt onset and
Onset/Pattern Gradual, crescendo; throbbing “tight”,
explosive resolution
“pressure”

Duration 4–72 hrs 30 min to 7 days 15–180 min 2–30 min; up to 40/day

Appearance Resting in quiet, dark room active or resting active or agitated Agitated and pacing

No Nausea; ANS: Ipsilateral

Nausea, Aura Lacrimation,
Associated pericranial lacrimation and
(visual/sensory/language), conjunctival injection,
Features muscle redness of eye.
photophobia, phonophobia rhinorrhea
tenderness Stuffy nose

15% prevalence; 3:1 F:M; Most common

Rare (0.1%); M:F = Rarest TAC; M=F; mean
Epidemiology onset <35 y/o; 75% have HA; 69–88%
4.3:1; smokers onset 34–41
prodrome lifetime

Cortical spreading
Myofascial Hypothalamic and Similar to cluster;
depression,
Pathophysiology nociceptor trigeminal autonomic unknown exact
trigeminovascular
sensitization reflex activation mechanism
sensitization, CGRP

NSAIDs, triptans, NSAIDs, 100% O₂,

Indomethacin (diagnostic
Acute Tx metoclopramide + acetaminophen intranasal/subQ
+ therapeutic)
prochlorperazine, rimegepant + caffeine sumatriptan

Topiramate, propranolol, Amitriptyline, Verapamil, short-term

Preventive Tx amitriptyline, CGRP inhibitors biofeedback, prednisone, Indomethacin daily
(rimegepant, eptinezumab) acupuncture topiramate

Osteopathic Treatments for Primary Headaches

Target Region Objective Techniques

Soft tissue, MFR, ME, FPR, rib raising,

Upper thoracic & rib dysfunction Balance autonomics, reduce tension
HVLA

Cervical spine (C0–C2) Eliminate mechanical/muscular contributors Soft tissue, OA MFR, ME, FPR, HVLA

Cranial strain / TMJ dysfunction Reduce strain on trigeminal system Cranial osteopathy, MFR/ME for TMJ

Lumbosacral & pelvis Address compensatory strain patterns Soft tissue, MFR, ME, HVLA, counterstrain

Stress management Decrease triggers Counseling, lifestyle modification

Preventive health Reduce risk of future illness Smoking cessation, exercise, screenings
 Common Secondary Headaches
Condition Key Features Diagnosis/Treatment

Electric shock-like pain in V2/V3, Dx: clinical; Tx: carbamazepine,

Trigeminal Neuralgia
triggered by innocuous stimuli oxcarbazepine, ± surgery

Subarachnoid Sudden "worst headache of life," ± neck Dx: non-contrast CT → LP

Hemorrhage (SAH) stiffness, ± LOC (xanthochromia); EMERGENT evaluation

New HA in elderly, scalp tenderness, Dx: temporal artery biopsy; Tx: urgent
Temporal Arteritis (GCA)
vision loss, ↑ESR steroids

Progressive headache, worse in Dx: MRI/CT; Tx: neurosurgical/oncologic

Intracranial Mass
morning, ± vomiting, focal neuro signs management

Obese female; daily diffuse HA, visual Dx: ↑ICP on LP, MRI; Tx: acetazolamide,
Pseudotumor Cerebri (IIH)
loss, papilledema weight loss

Carotid/Vertebral Artery Sudden neck pain, Horner’s syndrome Dx: CT/MR angiography; Tx:
Dissection (carotid), brainstem signs (vertebral) antithrombotics; EMERGENT referral

Aching lateral HA, worsens with

TMJ Headache Dx: exam; Tx: NSAIDs, dental guard, OMM
chewing; often misdiagnosed as OM
IV. “Red Flag” Headache Features (Suggest Secondary Etiology)
Red Flag Possible Cause

Sudden onset, maximal at start SAH

New HA > age 50 Temporal arteritis, mass lesion

Awakens from sleep ↑ICP, tumor

Positional change worsens HA ↑ICP, pseudotumor cerebri

Visual field defects, papilledema IIH, mass lesion

Fever, neck stiffness Meningitis, encephalitis

Neurologic deficits Stroke, mass lesion

Anticoagulation Intracranial hemorrhage

Known cancer Metastatic disease

Post-trauma Subdural/epidural hematoma

V. Clinical Approach to Headache
1.​ Detailed History and Physical Exam
2.​ Determine If Primary vs Secondary
○​ No neuro findings = likely primary; "red flag" = workup for secondary
3.​ Management, Treat based on diagnosis
○​ Primary: lifestyle + pharmacologic + OMM
○​ Secondary: urgent imaging/intervention
 Neuro 65, Traumatic Brain Injuries I
GCS ≤ 8: severe TBI; associated with coma → intubation and airway protection.

Primary vs. Secondary Brain Injury

Type Description

Primary Irreversible damage at time of impact (e.g., laceration, contusion, hemorrhage).

Secondary Preventable sequelae: ischemia, edema, ↑ ICP, hypoxia, hypotension.

Top 3 Causes of Secondary Brain Injury (highlighted only)

Cause Effects Treatment

↓ Cerebral perfusion, ↑
Hypotension ?
Ischemia & infarction

Hypoxia ↑ Ischemia & infarction Oxygen, airway management, SaO₂ > 90%

↑ ICP ↓ CPP, ↑ Ischemia & infarction Hyperventilation, mannitol/hypertonic saline, surgery

Monro-Kellie Doctrine: Cranial contents (brain + CSF + blood) must maintain a fixed volume.
●​ When compensatory mechanisms fail, ICP rises rapidly → herniation risk.

Cerebral Blood Flow (CBF)

●​ Major Determinant: Cerebral Perfusion Pressure (CPP)
●​ Formula: CPP = MAP – ICP (Goal CPP = 60–70 mmHg)

ICP, MAP, CPP, CBF Interactions

●​ ↑ ICP → ↓ CPP → ↓ CBF → ischemia
●​ ↓ MAP → ↓ CPP → ↓ CBF → ischemia
●​ Treatment Principles: Prevent hypotension and Reduce ICP

Major Consequence of ↑ ICP: Cerebral herniation → brainstem compression → death

Most Common Herniation: Uncal

●​ Ipsilateral pupillary dilation, Contralateral hemiparesis, Decreased consciousness

Cushing’s Triad: Indicates impending herniation; late but urgent sign in ↑ ICP
●​ Bradycardia, Hypertension, Irregular respirations

Hypotension and Hemorrhagic Shock in TBI

●​ 1) Shock not due to brain injury alone — search for other bleeding sources.
●​ 2) Scalp wounds can bleed profusely → volume loss & shock.

Most Important Imaging for Moderate/Severe TBI: Non-contrast head CT

Mannitol vs. Hypertonic Saline
●​ Indication: Acute ↑ ICP, impending herniation
●​ Mechanism: Osmotic diuresis → draws fluid from brain → ↓ ICP
●​ Mannitol: Monitor renal function; Hypertonic saline: Safer in hypotensive patients

PaCO₂ Goals in TBI

●​ No ↑ ICP: 35–45 mmHg; With ↑ ICP needing hyperventilation: 30–35 mmHg

Hyperventilation in TBI
●​ Indication: Signs of herniation
●​ Effect: ↓ PaCO₂ → cerebral vasoconstriction → ↓ ICP
●​ Danger: ↓ CBF → ischemia (only use briefly)

Surgical Intervention: Definitively reduces ICP, evacuates hematomas

Acute Danger in Scalp Laceration

●​ Severe blood loss → hemorrhagic shock; Treat: Hemostasis, fluids/blood

Skull Fracture Types

Fracture Type Definition / Risk Factors

Depressed Bone displaced inward; ↑ risk of infection, seizures

Linear Single crack; if over meningeal groove → risk of Epidural hematoma

Open Communicates with scalp laceration; DO NOT remove objects

Basilar Signs: Battle sign, raccoon eyes, CSF leak; need CT Bone

Diffuse Axonal Injury (DAI): High-speed deceleration → axonal shearing

●​ Prolonged coma without focal hemorrhage on CT;

Epidural Hematoma (EDH): Middle meningeal artery tear (temporal bone fracture)
●​ Lucid interval → rapid decline; Tx: Emergent surgical evacuation; biconvex on CT

Subdural Hematoma (SDH): caused by bridging veins

●​ Risk: Elderly, alcoholics (brain atrophy); CT: Crescent-shaped, crosses sutures

Subarachnoid Hemorrhage (SAH): caused by tearing of subarachnoid vessels

●​ CT: Blood in sulci/cistern, Vasospasm; Tx: Nimodipine (prevents vasospasm)

Intracerebral Hemorrhage (ICH): Cause by contusions coalescing into mass effect

●​ CT: Focal hyperdensity; Tx: Surgery if mass effect; ICP monitoring
 Neuro 66, Traumatic Brain Injuries II and Concussion
1. A GCS score of 13–15 = mild traumatic brain injury (mTBI), including concussion.

2. The two functional areas altered in a concussion are neurocognitive and motor function.

3. Four key summary features of concussion include:

●​ It is a functional brain injury, not structural, and is diagnosed clinically.
●​ Symptoms include headache, dizziness, poor balance, and cognitive issues
●​ Loss of consciousness is uncommon, and focal neurological signs are absent.
●​ Standard imaging (CT, MRI) shows no abnormalities

4. Red text symptoms include headache, dizziness, poor balance, fatigue, difficulty
concentrating, difficulty remembering, sleep disturbances.

5. The five general diagnostic criteria for concussion are:

●​ History of trauma to the head or body with transmitted force
●​ Symptoms that develop immediately or soon after the trauma
●​ A neurologic exam without focal deficits (focal findings suggest a more serious injury)
●​ Clinical assessment tools and exclude other potential diagnoses

6. Clinical assessment tools are helpful for diagnosis and tracking recovery but should not be
used alone to make or exclude a diagnosis.

7. Routine CT scanning is not indicated in uncomplicated mTBI.​

Need for CT include: GCS < 15, decreased level of consciousness, focal neurological
deficit, severe or worsening headache, prolonged unconsciousness/confusion

8. Biomarker testing (e.g., GFAP, UCH-L1) may help identify patients with mTBI who are at low
risk for intracranial lesions and thus may not need CT imaging.

9. Immediate assessment should focus on ABCs and C-spine clearance. Once stabilized, a
detailed neurologic, mental status, and physical exam should be performed.

10. A focal neurologic deficit in a patient with suspected concussion raises concern for a
more serious intracranial or spinal injury and mandates urgent imaging and stabilization.

11. Before an athlete can return to play, they must be asymptomatic, have a normal physical
and neurologic exam, and receive medical clearance.

12. If concussion is suspected:

●​ The athlete must be immediately removed from play (this is the most important
intervention after ABCs and C-spine stabilization).
●​ They must not return the same day and require medical evaluation and clearance.
13. Red flag symptoms within the first 24–48 hours that require immediate evaluation include:
worsening headache, vomiting, numbness or tingling, weakness, slurred speech, mental
confusion, drowsiness, or decreased level of consciousness.

14. Treatments to avoid in the first 48–72 hours include: no alcohol, narcotics, sleep aids,
and possibly NSAIDs (bleeding risk). These mask symptoms and worsen neurologic status.

15. During the first 24–48 hours, patients should undergo relative rest—early return to activities
of daily living, light walking, and limited screen time.​
The Return to Learn and Return to Sport processes can begin after 24–48 hours if
symptoms are mild or resolved. Must avoid activities with high risk of reinjury.

16. Return to sport process includes stepwise progression with each stage taking at least 24
hrs. If symptoms recur, athlete should stop and resume previous step after symptoms resolve.

17. Second impact syndrome occurs when a second concussion happens before the first
has fully healed, often within 7–10 days. This can lead to catastrophic brain swelling,
herniation, and death.

18. The two most common persistent post-concussive symptoms are headache and memory
problems.

19. The neuropathologic finding in Chronic Traumatic Encephalopathy (CTE) is abnormal

p-tau accumulation in a distribution distinct from other tauopathies.

20. TES (Traumatic Encephalopathy Syndrome) is a clinical syndrome associated with CTE.
●​ Core clinical features include memory/executive function deficits and emotional
dysregulation (e.g., rage, lability).
●​ Non-core features include psychiatric symptoms (depression, paranoia) and motor
signs (ataxia, parkinsonism).

21. The three key action steps in most concussion laws are:
1.​ Concussion education for coaches, parents, and athletes
2.​ Immediate removal from play after a suspected concussion
3.​ Medical clearance required before return to play
 Neuro 67, Pharmacology of Parkinson's Disease
I. Pharmacological Strategies in PD
Strategy Goal Drug Classes / Examples

Supply dopamine precursor Levodopa + Carbidopa,

↑ L-DOPA availability
(Dopamine can’t cross BBB) Entacapone, Tolcapone

↑ Central dopamine Inhibit dopamine breakdown MAO-B inhibitors, COMT inhibitors

↑ Extracellular Enhance release, block

Amantadine
dopamine reuptake

Stimulate dopamine Dopamine agonists:

Mimic dopamine
receptors Pramipexole, Ropinirole, Apomorphine

↓ ACh signaling Restore DA/ACh balance Antimuscarinics: Benztropine, Trihexyphenidyl

II. Mechanism of Action & Usage

1. Levodopa + Carbidopa ± COMT inhibitors
●​ MoA: L-DOPA crosses BBB → converted to dopamine in CNS.
●​ Carbidopa inhibits peripheral DDC → ↑ L-DOPA in the brain.
●​ COMT inhibitors (Entacapone, Tolcapone) inhibit L-DOPA metabolism.
●​ Use: Most effective for bradykinesia/rigidity; first-line in older adults.
●​ Note: patients experience decline in response during 3rd-5th year of therapy
2. MAO-B Inhibitors (Selegiline, Rasagiline, Safinamide)
●​ MoA: Block dopamine breakdown in CNS.
●​ Use: Monotherapy in early PD or adjunct to L-DOPA in advanced PD.
●​ Selegiline → amphetamine metabolites → insomnia risk.
●​ Rasagiline: 5x potency, no amphetamine-like effects.
3. COMT Inhibitors (Tolcapone, Entacapone, Opicapone)
●​ MoA: Prevent L-DOPA breakdown; Tolcapone crosses BBB.
●​ Use: Adjunct to L-DOPA to reduce "wearing off" (response fluctuations).
4. Dopamine Agonists
Drug Receptor Key Use/Notes

Pramipexole D3 Mono/combo therapy, fewer fluctuations

Ropinirole D2 Also for restless leg syndrome

Apomorphine D2 Rescue for "off" periods, subQ only

Rotigotine D3 Patch form for continuous delivery

Bromocriptine D2 (ergot) Rarely used; fibrosis risk

●​ Use: Mild symptoms, younger patients, delay L-DOPA (Fewer motor fluctuations.)
5. Amantadine
●​ MoA: ↑ dopamine release, ↓ reuptake; NMDA antagonist, MOA unclear
●​ Use: Mild symptoms, dyskinesia control.
 6. Antimuscarinics (Benztropine, Trihexyphenidyl)
●​ MoA: Block ACh to rebalance DA/ACh signaling.
●​ Use: improve tremor and rigidity in younger patients, little effect on bradykinesia
●​ Avoid in elderly: confusion, urinary retention.
7. Adenosine A2A Antagonist (Istradefylline)
●​ MoA: Reduces "off" time by blocking A2A receptors.
●​ Use: Adjunct to L-DOPA/carbidopa.
●​ Adverse: Dyskinesia, nausea, hallucinations.
8. Deep Brain Stimulation (DBS)
●​ When: Medication failure or intolerable side effects.
●​ Where: Subthalamic nucleus or globus pallidus internus.
●​ Use: Adjunct; reduces motor fluctuations.

III. Adverse Effects, Interactions, Contraindications

Class Adverse Effects Interactions / Contraindications

GI, cardiovascular, behavioral, dyskinesias and

L-DOPA + B6, MAO inhibitors, psychosis, glaucoma,
response fluctuations (choreoathetosis,
Carbidopa melanoma
wearing off rxns, on-off phenomenon)

COMT inhibitors Diarrhea, orange urine, Tolcapone = hepatotoxic SSRIs, stroke history, CVD

MAO-B inhibitors Insomnia (Selegiline), serotonin syndrome SSRIs, SNRIs, opioids, liver disease

Dopamine agonists N/V, orthostasis, hallucinations, impulse control MI, psychosis, peptic ulcer

CHF, seizures, sleep meds, alkalinizing

Amantadine Edema, livedo reticularis, confusion
agents

Antimuscarinics Dry mouth, blurred vision, confusion, constipation Glaucoma, BPH, MG, ileus

A2A antagonist Dyskinesia, hallucinations, nausea Psychosis, severe liver/renal disease

IV. Therapeutic Timing

Scenario Preferred Strategy

Mild, early PD (young) Dopamine agonists, MAO-B inhibitors, anticholinergics

Mild, early PD (older) Levodopa-carbidopa

Motor fluctuations COMT inhibitors, MAO-B inhibitors, Amantadine

Severe “off” periods Apomorphine

Resistant tremor Add antimuscarinic or DBS

Dyskinesias Reduce L-DOPA dose, add Amantadine

 Neuro 68, Pain Management
1. Define Integrative Pain Management
Patient-centered, evidence-informed approach to treating pain that combines conventional
medical treatments with complementary and lifestyle-based therapies.
●​ emphasizes whole-person care, considering physical, emotional, mental, spiritual, and
social factors contributing to the pain experience.

2. Recognize the multidimensional aspects of the pain experience and its related management
Pain is a biopsychosocial phenomenon. Effective pain management considers:
●​ Biological: tissue injury, inflammation, neurophysiology.
●​ Psychological: fear, anxiety, depression, catastrophizing.
●​ Social: work status, family support, socioeconomic factors.
Examples from the readings:
●​ Chronic low back pain may persist even after tissue healing and is worsened by
psychological distress or fear-avoidance behavior.
●​ Fibromyalgia involves CNS sensitization, altered neurotransmitters (e.g., GABA,
glutamate), and stress response dysregulation.
●​ Headache management: address sleep, stress, mood with pharmacologic treatment.

3. Indications, contraindications, risks of multimodal/integrative pain management

Modality Indications Contraindications / Cautions Risks

Exercise (e.g., tai chi, CLBP, fibromyalgia, Acute flare-up of injury or

Overexertion, falls
yoga) migraine prevention unstable joints

Mind-body (CBT, Fibromyalgia, CLBP, Non specific, may be limited by Rare emotional distress
mindfulness) headaches engagement in trauma survivors

Nutrition / Fibromyalgia, migraines, Food allergies, restrictive Nutritional imbalance if

Anti-inflammatory diet general wellness eating disorders poorly managed

Chronic pain (headache, Bleeding disorders, Bruising, infection, rare

Acupuncture
CLBP, fibromyalgia) anticoagulation pneumothorax

Manual therapy / Tension-type headache, Acute fractures, cancer in the Temporary soreness,
OMT / Massage LBP area, coagulopathy rare worsening

Pharmacologic Acute migraine, LBP GI disease, kidney dysfunction, GI bleed, renal injury,
(NSAIDs, triptans) flare cardiovascular risks rebound headache

CGRP inhibitors, Injection reactions,

Chronic migraine Hypersensitivity
botox constipation

Focus on therapeutic reviews from reading

 Neuro 69, Vitamin Deficiency and Excess in Neurologic Disease
1. Folic Acid and Neural Tube Defects (NTDs)
●​ Folic acid (Vitamin B9) deficiency is strongly associated with NTDs, including:
○​ Spina bifida and Anencephaly
●​ Critical window for folate: gestational days 15–28 (post-conception).
●​ Mandatory folic acid fortification of grains in the U.S. → 20–23% decline in NTD rates.
●​ High-risk populations: Latino women, those with MTHFR mutations, poor dietary
intake, GI disorders, and those on anticonvulsants (e.g., valproate, phenytoin).

2. Vitamins and Stroke Risk

●​ Elevated homocysteine is associated with increased stroke risk.
○​ Homocysteine is reduced by B6, B9 (folate), and B12.
●​ Folate supplementation is protective, particularly in populations with low dietary intake.
●​ Vitamin E: has antioxidant and antiplatelet properties; excess (>400 IU) may increase
risk of hemorrhagic stroke.
●​ Vitamin D: inverse relationship with ischemic stroke, but evidence is inconclusive.

3. Vitamins, Obesity, and Cognitive Impairment

●​ Low folate is associated with mild cognitive impairment and elevated homocysteine,
which contributes to dementia.
●​ Vitamin B12 deficiency: dementia, ataxia, memory loss, and other CNS symptoms.
●​ Vitamin D deficiency: associated with a 33% higher dementia risk in elderly.
●​ Obesity → dementia: inflammation, Leptin resistance, impairing neuronal signaling.

4. Wernicke-Korsakoff Psychosis & Thiamine (Vitamin B1) Deficiency

●​ Common: alcohol use disorder, starvation, bariatric surgery, hyperemesis gravidarum.
●​ Wernicke’s Encephalopathy (acute):
○​ Triad: delirium, ophthalmoplegia (nystagmus), ataxia
○​ Subtle presentations are more common; precipitated by glucose administration.
●​ Korsakoff Psychosis (chronic):
○​ Anterograde/retrograde amnesia, confabulation, normal conversation flow.
●​ Treatment: thiamine replacement (before glucose) to prevent irreversible damage.

5. Vitamin Etiologies for Peripheral Neuropathy

●​ Vitamin B12 deficiency:
○​ Posterior/lateral spinal column degeneration.
○​ Loss of vibration/proprioception, ataxia, symmetric paresthesia.
●​ Vitamin B6 (pyridoxine):
○​ Deficiency: neuropathy, glossitis, psychiatric symptoms.
○​ Associated with Isoniazid for TB – TQ
○​ Toxicity: doses >500 mg/day → sensory neuropathy.
●​ Thiamine (B1) deficiency: symmetrical distal sensory and motor neuropathy.
●​ Niacin (B3): deficiency causes pellagra (3 D’s: dermatitis, diarrhea, dementia)
 Neuro 70, Anti-seizure Drugs
1. Categories of Anti-Seizure Drugs
Based on Mechanism of Action:
1.​ Na⁺ Channel Blockers
○​ Phenytoin, Carbamazepine, Lamotrigine, Lacosamide
2.​ Ca²⁺ Channel Modulators
○​ Ethosuximide (T-type), Gabapentin, Pregabalin (α2δ)
3.​ GABA Enhancers
○​ Benzodiazepines, Phenobarbital, Vigabatrin, Tiagabine
4.​ Glutamate Inhibitors
○​ Perampanel (AMPA), Felbamate (NMDA)
5.​ Synaptic Vesicle Modulators
○​ Levetiracetam, Brivaracetam (bind SV2A)
6.​ Mixed / Broad-spectrum / Unknown
○​ Valproate, Topiramate, Zonisamide, Cannabidiol

2. Molecular Mechanisms of Action

Drug/Class Mechanism

Phenytoin Binds inactivated Na⁺ channels → ↑ AP threshold

Carbamazepine Na⁺ channel blocker; induces CYP450

Ethosuximide Blocks T-type Ca²⁺ channels (absence seizures)

Benzodiazepines ↑ GABA-A activity (↑ Cl⁻ influx)

Phenobarbital Prolongs GABA-A Cl⁻ channel opening

Vigabatrin Inhibits GABA transaminase

Tiagabine Inhibits GABA reuptake (GAT-1)

Levetiracetam Binds SV2A → ↓ glutamate release

Perampanel AMPA receptor antagonist

Topiramate Na⁺ blocker, enhances GABA, ↓ AMPA, weak CA inhibitor

Valproate Na⁺ and T-type Ca²⁺ block, ↑ GABA, inhibits GABA transaminase

Cannabidiol Multi-receptor; exact mechanism unclear

3. Therapeutic Uses
Condition Preferred Drugs

Focal Seizures Carbamazepine, Lamotrigine, Levetiracetam, Lacosamide

 Carbamazepine, phenytoin, valproate (all first line), phenobarbital +
Generalized Tonic-Clonic
primidone (second line), lamotrigine and topiramate (adjunct meds)

Absence Seizures Ethosuximide (1st line), Valproate

Myoclonic Seizures Valproate (1st line), Levetiracetam, Topiramate

Atonic / Lennox-Gastaut Valproate + Lamotrigine + Benzodiazepine; Topiramate, Felbamate

Status Epilepticus Diazepam/Lorazepam → Fosphenytoin → Phenobarbital

Trigeminal Neuralgia Carbamazepine

Bipolar Disorder Lamotrigine, Carbamazepine

Infantile Spasms (TSC) Vigabatrin

4. Adverse Effects, Drug Interactions, Contraindications

Drug Adverse Effects Key Interactions / Notes

Gingival hyperplasia, hirsutism, SJS, Nonlinear (zero-order) kinetics;

Phenytoin osteomalacia, megaloblastic anemia, CYP inducer
teratogenicity (Category D) CU in patients with absence seizures

Diplopia, ataxia, rash, hyponatremia, teratogenic

Carbamazepine CYP inducer; autoinduction
(NTDs), SJS (screen HLA-B*1502 in Asians)

GI upset, hepatotoxicity, pancreatitis, weight Inhibits metabolism of lamotrigine,

Valproate
gain, teratogenic (NTDs) phenobarbital

Lamotrigine Rash (slow titration to avoid SJS) Valproate ↑ lamotrigine levels

Ethosuximide GI upset, fatigue, headache, SJS (rare) ↓ clearance with valproate

Phenobarbital Sedation, cognitive impairment Avoid in absence seizures

Renally excreted – good in hepatic

Gabapentin Sedation, dizziness; few drug interactions
dysfunction

Levetiracetam Somnolence, irritability Minimal drug interactions

Cognitive dulling, weight loss, metabolic

Topiramate CA inhibition effects
acidosis, kidney stones, teratogen (cleft palate)

Perampanel Aggression, mood disturbances Long half-life

Vigabatrin Irreversible visual field loss Eye exams needed regularly

Benzodiazepines Sedation, tolerance, respiratory depression Use short-term due to tolerance

 Neuro 71, Demyelinating Neuropathology
1. Multiple Sclerosis (MS)
Pathophysiology
●​ Autoimmune demyelination of CNS white matter (oligodendrocytes).
○​ Shwann cells in PNS → if in PNS, likely won't affect CNS
●​ Triggered by environmental factors in genetically predisposed individuals (e.g.,
HLA-DRB1*1501, IL-2/IL-7R polymorphismes).
●​ Th1 and Th17 cells → cytokine release (e.g., IFN-γ), macrophage and leukocyte
recruitment; B cells and antibodies also play a role.
●​ Microscopy: active plaques or quiescent (inactive) plaques
●​ Luxol fast blue stain: Myelin is blue
Disease Patterns
●​ Relapsing-remitting (RRMS): 85–90%; episodes followed by remission.
●​ Secondary-progressive (SPMS): RRMS that transitions into steady progression.
●​ Primary-progressive (PPMS): Steady progression without relapses.
●​ Clinically Isolated Syndrome (CIS): First demyelinating episode with MRI lesions.
●​ Radiologically Isolated Syndrome (RIS): MRI findings without clinical symptoms.
Diagnostic Criteria → Clinical + MRI:
●​ Lesions separated in time (multiple episodes) and space (multiple CNS locations).
●​ T2/FLAIR hyperintensities, often periventricular (Dawson’s fingers).
○​ Gadolinium enhancement = active plaques.
●​ CSF: Oligoclonal IgG bands, mild protein elevation, occasional pleocytosis.
Characteristic Clinical Features
●​ Optic Neuritis: Monocular vision loss + pain with eye movement. (Marcus Gunn Pupil)
●​ Internuclear Ophthalmoplegia (INO): Lesion in MLF → impaired adduction with
contralateral abducting nystagmus.
●​ Lhermitte Sign: Electrical sensation down spine with neck flexion.
●​ Uhthoff Phenomenon: Worsening symptoms with heat.

2. Mimics of MS
Acute Disseminated Encephalomyelitis (ADEM)
●​ Monophasic, post-infectious autoimmune demyelination.
●​ Mostly children; fever, confusion, seizures, rapid progression (non-localizing findings)
●​ MRI: Multifocal, symmetric, bilateral white matter lesions.
●​ Histology: Perivenous demyelination.
●​ Treatment: IV corticosteroids.
Neuromyelitis Optica (NMO, Devic’s Disease)
●​ Antibody-mediated demyelination of optic nerves and spinal cord.
●​ Bilateral optic neuritis + spinal cord demyelination (≥3 vertebral segments).
●​ Aquaporin-4 IgG positive (specific).
●​ CSF: ↑ neutrophils.
●​ MRI: LETM (longitudinally extensive transverse myelitis), optic nerve enhancement.
○​ Lesions separated in space but not in time
3. Guillain-Barré Syndrome (GBS)
Pathogenesis
●​ Autoimmune segmental demyelination of peripheral nerves (PNS).
●​ Follows infection (e.g., Campylobacter jejuni) via molecular mimicry.
Clinical Presentation
●​ Symmetric ascending weakness + areflexia.
●​ May involve facial paralysis, sensory loss, and autonomic dysfunction.
●​ Risk of respiratory failure.
CSF Findings
●​ Albuminocytologic dissociation: ↑ protein with normal WBC count.
Treatment
●​ IVIG, plasmapheresis, respiratory support.
●​ Most recover within weeks to months.

4. Other Demyelinating Disorders

Charcot-Marie-Tooth (CMT), aka hereditary motor and sensory neuropathy
●​ Most common inherited peripheral neuropathy.
●​ Autosomal dominant; mutations in PMP22 or myelin/axon genes.
●​ Motor > sensory symptoms.
●​ Onset: Childhood.
●​ Clinical: Distal weakness, pes cavus, hammer toes.
●​ Histology: Onion bulb formations (repetitive demyelination/remyelination).

Leukodystrophies (Dysmyelinating Disorders)

Disease Defect Features Histology / Imaging

Galactocerebrosidas Infant onset; CNS + PNS

Krabbe Globoid cells
e deficiency demyelination

Toxic sulfatide buildup →

Metachromatic Arylsulfatase A
oligodendrocyte/Schwann Metachromatic staining
leukodystrophy deficiency
death

ABCD1 mutation → X-linked; boys with behavior Posterior white matter,

Adrenoleukodystrophy
↑ VLCFAs changes + adrenal failure sparring of U-fibers early

Osmotic Demyelination Syndrome (Central Pontine Myelinolysis)

●​ Rapid correction of hyponatremia → demyelination in the pons.
●​ Presents with: quadriplegia, dysarthria, diplopia, LOC.
●​ Histology: Myelin loss without inflammation; axons preserved.
●​ MRI: T2/FLAIR hyperintense lesion in the pons