Goljy 26: Nervous System and Special Sensory Disorders Flashcards
intracellular edema
water moves into cells
caused by:
1. dysfunctional Na+/K+-ATPase pump
2. Hyponatremia causing osmotic shift
extracellular edema
d/t increased vessel permeability
caused by:
1. acute inflammation
2. metastasis, trauma, lead poisoning
Why is a person with head trauma purposely hyperventilated?
- to produce respiratory alkalosis –> cerebral vessel constriction
- decreases risk of increased vessel permeability and edema
What effect do respiratory acidosis and hypoxemia have on cerebral vessels?
- vasodilation –> increased vessel permeability –> edema
Signs of increased intracranial pressure
- papilledema
- headache, projectile vomiting w/o nausea
- sinus bradycardia, hypertension
- potential for herniation
pseudotumor cerebri
- increased intracranial pressure without evidence of tumor/obstruction d/t decreased CSF resorption in arachnoid villi (equilibration in inflow/outflow eventually occurs)
- papilledema is present, no mental status change/focal neurologic signs
- MC young obese women, other risks: ATRA used for APML, hypothyroid, Cushing disease, BC pills, isotretinoin, tamoxifen
pseudotumor cerebri Sx, Dx, Tx
Sx: headache, rhythmic sound in one/both ears, diplopia, blurry vision
Dx: MRI - flattening of posterior globe
CSF pressure increased, decreased CSF protein
Tx: carbonic anhydrase inhibitor or systemic corticosteroids if visual disturbances present, lumboperitoneal shunt, optic nerve sheath fenestration
cerebral herniation
a complication of intracranial hypertension where portions of the skull become displaced through either openings in the dural partitions or openings of the skull
subfalcine herniation
- cingulate gyrus herniates under the falx cerebri
- herniation causes compression of the anterior cerebral artery
uncal herniation
- medial portion of the temporal lobe herniates through the tentorium cerebelli
- Can cause:
1. Compression of the midbrain –> Duret hemorrhage
2. Compression of CN III –> eye deviates down and out, pupil is dilated d/t compression of parasympathetic postganglionic fibers
3. compression of posterior cerebral artery –> hemorrhagic infarction of occipital lobe
tonsillar herniation
- cerebellar tonsils herniate into foramen magnum
- “coning” of cerebellar tonsils
- cardiorespiratory arrest
hydrocephalus
increase in CSF volume –> enlargement of ventricles
production and movement of CSF
- produced by choroid plexus in ventricles
- exists fourth ventricle thru foramina of Luschka and Magendia and enters subarachnoid space
- reabsorbed by arachnoid villus into dural venous sinuses
Communicating hydrocephalus
- open communication btwn ventricles and subarachnoid space
- Causes:
1. increased CSF production
2. obstruction in reabsorption of CSF by arachnoid villi
Noncommunicating hydrocephalus
- obstruction of CSF flow out of ventricles
- Causes:
1. stricture of aqueduct of Sylvius - MCC in newborns –>paralysis of upward gaze
- pineal gland tumor
2. Tumor in fourth ventricle
3. scarring at base of brain
4. colloid cyst in 3rd ventricle
5. various developmental disorders
Clinical findings in hydrocephalus
Newborns: ventricles dilate and enlarge head circumference
Adults: ventricles enlarge but NO increase in head circumference
hydrocephalus ex vacuo
- dilated appearance of the ventricles when the brain mass is decreased from cerebral atrophy, eg. Alzheimer’s
Normal pressure hydrocephalus
Dilated ventricles and “wet wide and wacky” sx:
- urinary incontinence
- wide based gait
- dementia
Causes:
idiopathic
secondary to subarachnoid hemorrhage, intracranial surgery, trauma
Pathogenesis of normal pressure hydrocephalus
- subarachnoid space volume is increased
- ventricular dilation is out of proportion to sulcal atrophy
- wide based gait and urinary incontinence d/t stretching of sacral nerve fibers near dilated ventricle
- dementia d/t stretching of limbic fibers near dilated ventricle
normal pressure hydrocephalus dx and tx
Dx: MRI shows ventriculomegaly, sulcal atrophy
Large volume of CSF is removed at lumbar puncture, symptoms improve w/ removal of fluid
Tx: ventriculoperitoneal or ventriculoatrial shunt
Neural tube defect
- Failure of the fusion of the lateral folds of the neural plate
- Rupture of a previously closed neural tube
- Maternal folic acid levels must be adequate BEFORE pregnancy to prevent open neural tube defects
Maternal findings in neural tube defect
Increased maternal AFP in serum and/or amniotic fluid in anancephaly, meningocele, or myelomeningocele but NOT spina bifida occulta
Anancephaly
- complete absence of the brain
- frog-like appearance
- open spinal canal
- maternal polyhydramnios
Spina bifida occulta
- defect in closure of the posterior vertebral arch
- dimple or tuft of hair in the skin overlying L5-S1
meningocele
- spina bifida with cystic mass containing meninges
- MC in lumbosacral region
meningomyelocele
- spina bifida with cystic mass containing meninges and spinal cord
- MC in lumbosacral region
Arnold-Chiara malformation
- caudal extension of the medulla and cerebellar vermis through foramen magnum
- noncommunicating hydrocephalus
- platybasia
- a/w meningomyelocele, syringomyelia
- Tx: decrompression surgery
Dandy-Walker malformation
- partial or complete absence of the cerebellar vermis
- cystic dilation of the fourth ventricle
- noncommunicating hydrocephalus
- Tx: shunt to treat hydrocephalus
syringomyelia
- degenerative disease of the spinal cord
- Sx usually appear in 3rd of 4rd decade
- fluid-filled cavity (syrinx) within cervical spinal cord
- produces cervical cord enlargement
- cavity expands and causes degeneration of spinal tracts
Pathogenesis of syringomyelia
- obstruction of outflow from fourth ventricle
- birth injury
Clinical findings in syringomyelia
- disruption of the crossed lateral spinothalamic tracts –> pain and temp lost in the hands, tactile sense preserved
- destruction of anterior horn cells –> atrophy of intrinsic muscle of the hands, often confused with ALS
- Charcot joint in shoulder, elbow, or wrist
Dx and Tx of syringomyelia
Dx: MRI shows enlarged cervical cord and a cystic cavity
Tx: drainage of syrinx slows progression
Phakomatoses
- neurocutaneous syndromes including:
1. disordered growth of ectodermal tissue
2. malformationf or tumors of the CNS
Neurofibromatosis
AD w/ incomplete penetrance, no gender predominance
- Type 1: MC, mutation on chromosome 17 coding for neurofibromin
- Type 2: mutation on chromosome 22 coding for merlin
NF1
- cafe au lait spots
- optic gliomas
- Lisch nodules
- axillary and inguinal freckling
- mild scoliosis
- pigmented plexiform neurofibromas
- pigmented cutaneous/subcutaneous neurofibromas
a/w: pheochromocytoma, Wilms tumor, juvenile CML
NF2
a/w bilateral acoustic neuromas (CN8 benign tumor –> hearing loss, tinnitis), meningiomas, spinal schwannomas, juvenile cataracts
Tuberous sclerosis
AD, mental retardation and seizures beginning in infancy
- angiofibromas on the face
- hypopigmented skin lesions called shagreen patches/ash leaf spots
- subungal or periungal fibromas
- hamartomas: astrocyte proliferations, angiomyolipomas in kidneys, rhabdomyoma in the heart
Sturge- Weber syndrome
- somatic mosacism or sporadic
- vascular malformation on the face in trigem nerve distribution
- some patients have ipsilateral AV malformation in meninges
cerebral contusion
permanent damage to small blood vessels and the surface of the brain, most often secondary to an acceleration-deceleration injury
Coup injury
occurs at site of impact
Contrcoup injury
occurs opposite the site of impact, MC tips of frontal and temporal lobes
epidural hematoma
- arterial bleed creates a blood-filled space between the bone and dura
- caused by a fracture of the temporoparietal bone –> severance of the middle meningeal artery
- increased ICP –> herniation and death
- Dx: CT
- hematoma rarely crosses suture line
- Tx: burr holes to relieve pressure
subdural hematoma
- venous bleeding between the dura and arachnoid membranes
- MC d/t blunt trauma, also: medical anticoagulation, hemophilia, child abuse, spontaneous
- Risk factors: old people and alcoholics with brain atrophy
- tear in bridging veins between brain and dural sinuses are torn, causes venous blood clot
- herniation and death, chronic: dementia
- Tx: burr holes to relieve pressure
3 categories of cerebrovasular diseases:
- thrombosis
- infarction
- hemorrhage
Causes of cerebrovascular disease:
- Reduced blood supply and O2 of tissue
- CNS hemorrhage from rupture of cerebral vessels
Global hypoxic injury
Causes: cardiac arrest, hypovolemic shock, septic shock, CO poisoning
Complications: cerebral atrophy (necrosis of neurons in layers 3, 5, 6 of cerebral cortex), Watershed infarcts at the junctions of arterial territories, stroke
Stroke
sudden loss of blood circulation to an area of the brain resulting in a loss of neurologic function
- risk increases w/ age
Atherosclerotic stroke
MC type of stroke
- ischemic type of stroke caused by a platelet thrombosis that develops over a disrupted atherosclerotic plaque
- Common locations: MCA, internal carotid artery near bifurfaction, basilar artery
- Prevention: aspirin, clopidogrel
Gross/microscopic findings in atherosclerotic stroke
- Develops at the periphery of the cerebral cortex –> pale infarct
- Swelling of the brain, loss of demarcation btwn grey and white matter, myelin breakdown
- Gliosis
- Cystic area develops after 10 days-3 weeks d/t liquefactive necrosis
Transient ischemic attack
Transient episode of neurologic dysfunction caused by focal brain/spinal cord/retinal ischemia without infarction
amaurosis fugax
a retinal TIA caused by microembolization of atherosclerotic material to a bifurcation of the retinal arteries
Tx of TIA
- Antithrombic therapy
- Antiplately therapy
- possible carotid endarectomy/stenting
Strokes involving MCA
- contralateral hemiparesis and sensory loss in the face and upper extremity
- expressive aphasia if Broca’s area is involved in L hemisphere
- visual field defects
- head and eyes deviate toward site of lesion
Strokes involving ACA
Contralateral hemiparesis and sensory loss in lower extremity
Strokes involving vertebrobasilar arterial system
- vertigo, ataxia
- ipsilateral sensory loss in the face
- contralateral hemiparesis and sensory loss in trunk and limbs
Embolic stroke
- Ischemic type of stroke due to embolization
- Emboli MC originate from L side of heart
- produces a hemorrhagic infarction (MC in MCA, reperfusion after lysis of embolic material –> hemorrhage)
Sources of emboli
- Mural thrombi in LV after AMI, aortic/mitral valve vegetations, L. atrium in a fib
- A fib d/t thrombus formation in LA from stasis of blood
- “Shower” embolization (emboli blocking numerous small vessels)
Intracerebral hemorrhage
Most often d/t stress imposed on vessels by hypertension
- branches of lenticulostriate vessels develop Charcot-Bouchard microaneurysms
- rupture of aneurysms –> intracerebral hemorrhage
Common sites of intracerebral hemorrahage
Basal ganglia, thalamus, pons and cerebellar hemispheres
Slit hemorrhage
A/w hypertension
Rupture of small caliber penetrating vessels, producing hemorrhages that resorb blood, leaving slit-like spaces with a brownish-red pigment
Subarachnoid hemorrhage
- Majority secondary to rupture of berry aneurysm
- Can also be d/t bleeding from an AV malformation
Berry aneurysm
yum yum berries
Risk factors: normal hemodynamic stress, hypertension, coarctation of aorta, atherosclerosis, smoking
Most develop at junctions of communicating branches with main cerebral artery - junctions lack internal elastic lamina and smooth muscle
MC site is junction of the anterior communicating branch with ACA
Rupture releases blood into subarachnoid space
Blood in CSF is broken down into bilirubin pigment –> xanthochromia
Clinical findings in subarachnoid hemorrhage
“Worst headache ever”
Nuchal rigidity from blood irritating meninges
50% mortality
Complications: further hemorrhage, hydrocephalus, neurologic defects
Lacunar infarct
- Cystic area of microinfarction
Dx of stroke
CT scan without contrast, distinguishes hemorrhage from nonhemorrhagic stroke
Tx of stroke
Acute: Thrombolytic therapy in thromboembolic strokes (
Pathogenesis of CNS infections
- Hematogenous (MC)
- Traumatic implantation
- Local extension from nearby infection
- Ascent via peripheral nerve
Meningitis
- Inflammation of pia mater covering the brain
- Usually d/t hematogenous spread
Pathogenesis of bacterial meningitis
Adherence of bacteria to mucosa of nasopharynx >
Bacteremia >
Translocation through the BBB using bacterial lysins >
Bacterial in the subarachnoid space attract neutrophils >
Acute meningitis
Risk factors for bacterial meningitis in kids
- undernutrition, otitis media
- pneumonia, immunodeficiency
- viral infection, sickle cell
- craniofacial abnormality
Viral meningitis
Mostly fecal-oral, respiratory less common
Clinical findings and complications of meningitis
Clinical: Fever, nuchal rigidity, headache
Complications: Seizures, focal neurolog deficits, cranial nerve palsies, sensorineural hearing loss, communicating and noncommunicating hydrocephalus
Lab findings in viral meningitis
- Increased CSF protein
- Increased total CSF leukocyte count (lymphocytes)
- Normal CSF glucose
Lab findings in bacterial meningitis
- Increased CSF protein
- Increased total CSF leukocyte count (neutrophils)
- Decreased CSF glucose
Lab findings in fungal meningitis
- Increased CSF protein
- Increased total CSF leukocyte count (lymphocytes)
- Decreased CSF glucose
Encephalitis
- Inflammation of the brain
- Fever, headache, impaired mental status, drowsiness
- Meningoencephalitis
Cerebral abscess
- Either spreads from an adjacent focus of infection OR hematogenous spread
- Single or multiple lesions
Demyelinating disorders pathogenesis
- Destruction of normal myelin
- Production of abnormal myelin
- Destruction of oligodendrocytes
Multiple sclerosis
- MC demyelinating disease, MC in females 20-40
- An autoimmune disease with genetic (HLA-DR2) and environmental (microbial pathogens, vitamin D, sun exposure) factors
Pathogenesis of MS
- CD4+ TH1 cells and TH17 cells react against self myelin antigens (type IV hypersensitivity)
- CD4+ TH1 cells secrete IFN-gamma–> activates macrophages, TH17 releases cytokines to recruit neutrophils + monocytes
- Leukocytes + TNFa attack myelin sheath and oligodendrocytes –> demyelination
- Antibodies produced by autoreactive B cells are directed towards myelin sheath and oligodendrocytes as well (type II hypersensitivity)
Gross and microscopic findings in MS
- Demyelinating plaques in white matter of brain/spinal cord, white matter looks like grey matter
- Inflammatory infiltrate in plaques is composed of CD4+ T-cells, monocytes, and microglial cells w/ phagocytosed lipid
Clinical findings in MS
- Episodic course w/ acute relapses and remissions
- Sensory dysfunction: paresthesias, loss of pain, temp, vibratory sensation
- UMN dysfunction: spasticity, increased DTRs, muscle spasms, Babinski, weakness
- Autonomic dysfunction: urge incontinence, sexual dysfunction, bowel motility probs
- Optic neuritis
- Cerebellar ataxia
- Scanning speech
- Intention tremor, nystagmus
- Bilateral internuclear opthalmoplegia (demyelinated MLF)
- Flexion of neck –> electrical sensation down spine
Lab findings in MS
- Increased CSF leukocyte count
- Increased CSF protein
- Increased CSF MBP
- Normal CSF glucose
- High-res electrophoresis: oligoclonal bands (sign of demyelination)
- MRI sensitive to demyelinating plaques
Dx and Tx of MS
Dx: spinal tap, MRI with gadolinium
Tx: Acute relapse: high dose methylprednisolone
Chronic: DMARDs, monoclonal antibody, cytotoxic drugs
Central pontine myelinolysis
- MC in alcoholics w/ hyponatremia
- Rapid IV correction causes demyelination in basis pontis
- Tx: supportive
Group B strep neonatal meningitis
- Gram + coccus
- MCC neonatal meningitis
- Spreads from focus of infxn in maternal vagina
- Tx: penicillin G or ampicillin
E. coli neonatal meningitis
- Gram - rod
- 2nd MCC neonatal meningiti
- Tx: ceftazidime + gentamicin
Listeria neonatal meningitis
- Gram + rod, tumbling motility, actin rockets
- Soft cheese and hot dogs
- Tx: ampicillin + gentamicin
Strep pneumoniae meningitis
- Gram + diplococcus
- MCC meningitis in patients over 18
- Tx: ceftriaxone + vanc + dexamethasone
Neisseria meningitidis meningitis
- Gram - diplococcus found in posterior nasopharynx
- MCC meningitis in people under 18
- Tx: ceftriaxone
- prophylaxis: cipro/rifampin/ceftriaxone
Mycobacterium tuberculosis meningitis
- Complication of primary TB
- Involves base of brain
- Vasculitis and scarring
- Tx: isoniazid, rifampin, ethambutol, pyrazinamide, dexamethasone
Trepona pallidium meningitis, encephalitis, myelitis
- Gram - spirochete
- Types of neurosyphilis: Meningovascular, General paresis, Tabes dorsalis
Tx: penicillin G
Cryptococcus neoformans meningitis, encephalitis
- Immunocompromised host
- MC fungal infxn in AIDS
- Budding yeasts visible with India ink
Tx: fluconazole non-AIDS, amphotericin + flucytosine
Mucor species frontal lobe abscess
Occurs in DKA, spreads from frontal sinuses
Tx: amphotericin B
Naegleria fowleri meningoencephalitis
- Protozoa
- Involves frontal lobes
- Contracted by swimming in freshwater lakes
- Tx: amphotericin B
T. brucei encephalitis
- Protozoa
- Transmission from bite of tsetse fly
- Diffuse encephalitis, starvation MC death
- Dx: trypanosomes in blood, CSF; blood test
- Tx: pentamidine early, melarsoprol in encephalitis stage
Taenia solium cystericercosis
- Helminth transmitted by pigs
- Patient eats food or water containing eggs –> larval form invades brain –> calcified cysts cause seizures and hydrocephalus
- Tx: albenzadole + dexamethasone
T. gondii encephalitis
- Protozoa
- MC CNS space-occupying lesion in AIDS, ring-enhancing lesions on CT
- Congenital toxoplasmosis produces basal ganglia calcification
- Tx: pyrimethamine + sulfadiazine + leucovorin
Leukodystrophies
Inborn errors of metabolism
Adrenoleukodystrophy
- XR disorder
- Enzyme deficiency in B-oxidation of fatty acids in peroxisomes –> accumulation of long chain fatty acids
- generalized loss of myelin in brain, adrenal insufficiency
Metachromatic leukodystrophy
AR lysosomal storage disease
- deficiency of arylsulfatase A resuls in accumulation of sulfatides
Krabbe disease
- AR LSD
- Galactocerebroside B-galactocerebrosidase deficiency, leads to accumulation of galactocerebroside
- Brain shows large multinucleated histiocytic globoid cells
Alzheimer disease epidemiology
- MCC dementia, 3 types:
1. sporadic late onset type (MC)
2. sporadic early onset type (related to apolipoprotein E)
3. familial early onset type (mutations of APP on chromosome 21, presenilin 1 on chromosome 14, presenilin 2 on chromosome 1) - Prevalence increases with age
- Down syndrome has strong a/w Alzheimers
Where does B amyloid damage neurons?
- medial temporal lobe
- frontal cortex esp. entorhinal cortex, hippocampus
- occipital lobe spared
Role of activated glycogen synthase kinase-3B in neurotoxicity of B amyloid
- Activation of GSK causes phosphylation of AB –> neurotoxic
- Phosphorylated AB has positive feedback on GSK
- Initial activation of GSK traced to dysfunction within Wnt
- Normal Wnt signaling pathway inactivates GSK, preventing phosphorylation of AB
- When Wnt is dysfunctional, GSK stays activated –> phosphorylation of AB –> neurotoxicity
How does AB stain?
Stains positive with Congo red, has apple-green birefringence with polarization
What is AB a metabolic product of?
- APP
- APP normally coded for on chromosome 21
- Defects in metabolism of APP –> increase in AB
- a-secretases cleave APP into fragments that cannot produce AB
- B- secretases followed by g-secretases cleave APP into fradments that are converted to AB
Insulin degrading enzyme
- involved in the clearance of AB
- insulin resistance syndromes have increased risk for Alzheimers
Role of tau protein in Alzheimers
- Normal fxn is to main microtubules in neurons
- Activated GSK enhances hyperphosphorylation of tau protein –> protein changes shape into NF tangles in cytoplasm
How are NF tangles visualized?
Silver stain
What do NF tangles do?
Produce neuronal dysfunction including death of the neuron
PIN1 enzyme
Strips excess phosphate molecules from NF, restoring it to its original shape
- Deficient in some cases of Alzheimers
Gross and microscopic findings in Alzheimers
- Cerebral atrophy with dilation of ventricles
- NF tangles in cytoplasm of neurons
- Senile plaques
- Amyloid angiopathy
- Confirmation of AD requires postmortem exam of brain
Clinical findings in Alzheimers
- Decline in short term memory
- loss of smell
- Reduced ability for self care
- No focal neurologic deficits early in disease
- pts usually die from infxn
Dx, Tx of Alzheimers
- presumptive dx made with mental status testing
- PET used for DDx of dementia
Tx: Cholinesterase inhibitors, Memantine
Parkinsonism
- a group of disorders that alter dopaminergic pathways involved in voluntary muscle movement
What part of the brain is involved in voluntary muscle movement?
The striatal system, includes: substantia nigra, caudate, putamen, globus pallidus, subthalamus, thalamus
What is the principal NT of the nigrostriatal tract?
DOPAMINE
- connects the substantia nigra with the caudate and putamen
Causes of Parkinsonism
- idiopathic (MC)
- encephalitis, ischemia
- Chronic CO poisoning
- Wilson disease
- Addiction to MPTP
- Antipsychotic drugs
Pathophys of Parkinson disease
- Degeneration/depigmentation of neurons in the substantia nigra
- Causes deficiency of dopamine
- Most cases are sporadic
Clinical findings in Parkinson disease
- Muscle rigidity (bradykinesia, cogwheel rigidity)
- Resting tremor (“pill rolling”, illegible handwriting)
- Expressionless face, stooped posture
- Difficulty in initiating first step, shuffling gait
- Blepharospasm, postural instability
- Commonly have severe seborrheic dermatitis
- Dementia in some cases
Tx for Parkinson disease
- avoid drugs that worsen Parkinsonism (neuroleptics, antiemetics, MAOIs)
- Levodopa
- Carbidopa, benserazide - dopa decarboxylase inhibitor
- Bromocriptine, pergolide - dopamine agonist
- Selegiline, rasagiline - inhibit MAO-B
- Surgical procedures
Huntington disease
- AD trinucleotide repeat disorder (CAG) involving chromosome 4
- delayed appearance of Sx until age 30-40
- no gender difference
- Atrophy/loss of striatal neurons (caudate, putamen, globus pallidus)
Clinical findings in Huntingtons
- Chorea
- Oculomotor abnormalities
- Parkinsonism in later stages
- Depression
Dx and Tx of Huntingtons
Dx: genetic testing, imaging studies show atrophy of caudate and putamen
Tx: supportive :(
Friedreich ataxia
- AR trinucleotide repeat disorder (GAA)
- Frataxin deficiency –> impaired mitochondrial iron homeostasis –> cells more prone to apoptosis
- Sites of degeneration: dorsal root ganglia, posterior columns, spinocerebellar tract, lateral corticospinal tracts, large sensory peripheral neurons
- Hypertrophic cardiomegaly
- T1DM
Clinical findings in Friedreich ataxia
- Progressive gait ataxia
- Loss of deep tendon reflexes, initially at ankles
- Loss of vibratory sensation and proprioception
- Muscle weakness in legs
Dx and Tx of Friedreich ataxia
Dx: Genetic testing, MRI shows spinal cord atrophy
Tx: supportive :(
ALS
- degenerative disease involving loss of upper and lower motor neurons
- Sx usually appear between age 40-60
- Most cases are sporadic
- Possibly d/t mutated or misfolded superoxide dismutase 1 or misfolded leading to apoptosis of neurons
Clinical findings in ALS
- UMN signs: Spasticity, Babinski
- LMN signs: Muscle weakness beginning with atrophy of intrinsic muscles of hands, eventual paralysis of respiratory muscles
- no sensory changes
- preservation of bowel and bladder fxn
ALS Dx and Tx
Dx: electromyography and nerve conduction studies
Tx: Riluzole (glutamate antagonist), average survival time is 3-5 years
Werdnig-Hoffman disease
Lower motor neuron disease that occurs in children
Wilson disease
- AR defect of copper excretion in bile
- Defect in incorporation of copper into ceruloplasmin –> liver cirrhosis, excess free copper in blood
- CNS findings: atrophy and cavitation of basal ganglia, esp globus pallidus + putamen
- parkinsonism, chorea, dementia
Acute intermittent porphyria
- AD defect in porphyrin metabolism
- Deficiency of uroporphyrinogen synthase
- Proximal increase in porphobilinogen and ALA
- Heme has a negative feedback relationship with ALA synthase, so decrease in heme –> porphyric attack!!!
What is super spooky about pee in acute intermittent porphyria
When you first void, urine is COLORLESS
Exposure to light oxidizes PBG to porphobilin producing PORT-WINE COLOR
Classic “window sill test”
Clinical findings in acute intermittent porphyria
- Recurrent severe abdominal pain simulating acute abdomen –> patient has “bellyful of scars” (wut)
- Psychosis, peripheral neuropathy, dementia
Dx, Tx of acute intermittent porphyria
Dx: Enzyme assay in RBCs
Tx: Avoid drugs that precipitate attacks, carbo loading with glucose to inhibit ALA synthase
Vitamin B12 deficiency
Subacute combined degeneration of the spinal cord (posterior column and lateral corticospinal tract demyelination)
- dementia, peripheral neuropathy
CNS findings in alcohol abuse
- Cortical and cerebellar atrophy
- Central pontine myelinolysis
- Wernicke-Korsakoff syndrome
- Tx: Thiamine supplement
Wernicke-Korsakoff syndrome
- MC d/t thiamine deficiency
- Hemorrhages of small vessels w// hermosiderin deposits in the mammillary bodies and walls of 3rd and 4rd ventricles
- Neuronal loss, gliosis
- Wernicke encephalopathy (reversible)
- Korsakoff psychosis
Wernicke encephalopathy
Reversible: confusion, ataxia, nystagmus, opthalmoplegia
Korsakoff psychosis
- Advanced irreversible stage of Wernicke encephalopathy targeting limbic system
- Anterograde amnesia
- Retrograde amnesia
- Confabulation, hallucinations
Primary brain tumors in adults
- Most ABOVE tentorium cerebelli
- In order from greatest freq to least: GBM, meningioma, ependymoma
Primary brain tumors in children
- 2nd MC cancer in kids
- Most BELOW tentorium cerebelli
- In order from greatest freq to least: Cystic cerebellar astrocytoma, medulloblastoma, brainstem glioma
Risk factors for brain tumors
Turcot syndrome, neurofibromatosis, cigarette smoking
General clinical findings in brain tumor
- Headache: worse during night, a/w nausea + vomiting
- Seizures
- Signs/Sx intracranial HTN
Imaging studies for brain tumor
- MRI w/ gadolinium enhancement
- CT if calcium or hemorrhage is present
- fMRI for lesions in vital areas
- PET
Tx for brain tumors
Surgery, irradiation, chemo
Astrocytoma
- Accounts for ~70% of all neuroglial tumors
- Usually involves frontal lobe in adults, cerebellum in kids
- Grades I and II are low grade, III and IV are high grade
Glioblastoma multiforme
- High grade astrocytoma, may arise de novo OR from dedifferentiation of a low-grade astrocytoma
- Hemorrhagic tumor: multifocal areas of necrosis and cystic degeneration, commonly crosses corpus callosum
- May seed neuraxis via CSF, rarely mets outside CNS
- Generally shit prognosis
Meningioma
- MC benign brain tumor in adults
- MC in females (tumor has estrogen and progesterone receptors), some have androgen receptors
- Derived from meningothelial cell within arachnoid membrane that lines but is not adherent to the dura: MC has parasagittal location; other sites are olfactory groove and lesser wing of sphenoid
- A/W NF2, history of radiation
- Firm tumors that may indent surface of brain, causes increased bone density
- swirling masses of meningothelial cells encompass psammoma bodies
- New-onset focal seizures
Enpendymoma
- Benign tumor derived from ependymal cells
- Arises in cauda equina in adults, 4th ventricle in kids (can produce non-communicating hydrocephalus)
Medulloblastoma
- Malignant small cell tumor, primarily in kids
- Arises from external granular cell layer of cerebellum
- Often seeds neuraxis and invades 4th ventricle
Oligodendroglioma
- Benign tumor derived from oligodendrocytes, primarily in adults
- Frontal lobe tumor that frequently calcifies
CNS lymphoma
- Majority are metastatic high grade B-cell non Hodgkins lymphomas
- Primary CNS lymphomas: MC a/w AIDS, also: EBV-mediated B-cell lymphomas
Most common cancer in the brain
- Metastasis!
- In order of decreasing frequency: lung, breast, skin, kidney
Peripheral neuropathy
- Associated with demyelination and axonal degeneration
- Demyelination is often segmental –> sensory change often in “glove and stocking” distibution
- Axonal degenerations –> muscle fasciculations, atrophy
Charcot-Marie-Tooth Disease
- MC hereditary neuropathy, AD
- Peroneal nerve neuropathy –> causes atrophy of muscles in lower legs, legs have “inverted bottle” appearance
- Tx: supportive
Guillain-Barré Disease
- MC acute peripheral neuropathy
- MCC acute flaccid paralysis
- Predominantly motor involvement
- Autoimmune demyelination syndrome involving nerve roots and peripheral nerves
- Common preceding infections: M. pneumoniae pneumonia, Campylobacter jejuni enteritis, viral infections
Sx of Guillain-Barré
- Rapidly progressive ascending motor weakness usually starting at proximal muscles and moving distally
- Danger of respiratory muscle paralysis and death
- Depressed or absent deep tendon reflexes in arms and legs
- Glove and stocking paresthesias/anesthesia
Lab findings in Guillain-Barré
- Increased CSF protein, oligoclonal bands present on hi-res electrophoresis
- CSF glucose, cell count normal
Dx, Tx, Prognosis of Guillain-Barré
Dx: Spinal tap w/ increased CSF protein, electromyography + nerve conduction studies
Tx: Infusion IVIG or plasma exchange, mechanical vent if necessary
Prognosis: 5-10% mortality, full recovery 60%, residual weakness 15% (these numbers don’t add up wtf)
Diabetes mellitus neuropathy
- MCC peripheral neuropathy, d/w osmotic damage of Schwann cells
Idiopathic Bell Palsy
- LMN palsy causing unilateral facial paralysis
- Inflammatory reaction of facial nerve
- May be associated w/ HSV, HIV, sarcoidosis, Lyme disease (often bilateral), pregnancy
Sx of LMN Bell palsy
- ipsilateral upper and lower face involvement
- drooping of corner of mouth
- difficulty speaking
- inability to close eye
- inability to wrinkle forehead
- hyperacusis in some cases
Sx of UMN Bell Palsy
- Contralateral lower face involved
- Contralateral upper face spared
Drugs that cause peripheral neuropathy
Vincristine, hydralazine, phenytoin
Vitamin deficiencies that cause peripheral neuropathy
Deficiency of thiamine, B12, pyridoxine
Tx of peripheral neuropathies
- Antiseizure meds: gabapentin, carbamazepine
- Lidocaine patch
- Tricyclic antidepressants: amitriptyline, nortriptyline
Schwannoma
- Benign tumor derived form Schwann cells
- CN V and VIII may be involved
- Spinal nerve roots, peripheral nerves may be involved
Acoustic neuroma
- Schwannoma of CN VIII
- MC located in cerebellopontine angle
- Encapsulated tumors, usually unilateral, alternating dark + light areas under microscope
- Sx: associated w/ NF2 (bilateral), tinnitus, sensorineural deafness, sensory changes in CN V d/t nerve impingemtn
- Tx: surgery
Arcus senilis
- MC in elderly
- Grey-opaque ring at corneal margin
- Cholesterol deposits in corneal stroma, may indicate hypercholesterolemia if under
Opthalmia neonatorum
COnjunctivitis in newborn
Pathogens: Gonorrhea (first week), Chlamydia (2nd week)
Tx: ceftriaxone (gon), erythromycin (chlam), erythromycin eye drops for irritation
Bacterial conjunvtivitis
- Purulent conjunctivitis, pain but no blurry vision
- Pathogens: Staph aureus, Strep pneumoniae, Haemophilus influenzae
- Tx: gatifloxacin drops
Viral conjunctivitis
- Watery exudate
- Adenovirus: viral cause of pinkeye, painful periauricular adenopathy, no tx
- HSV1: keratoconjunctivitis with dendritic ulcers noted with fluorescein staining, tx: trifluridine opthalmic
Allergic conjunctivitis
- Seasonal itching of eyes
- Tx: antihistamine opthalmic solutions, olopatadine
Acanthamoeba infection
- Severe keratoconjunctivitis in patients who do not clean their contacts properly
- Tx: propamidine + polymyxin/neomycin/granmicidin opthalmic
Stye
- Infection of the eyelid most commonly d/t staph aureus
- Tx: hot packs, dicloxacillin
Chalazion
- Granulomatous inflammation involving the meibomian gland in the eyelid; usually disappears on its own w/in 2 months
- Tx: if it doesn’t go away on its own, intralesional corticosteroid injection or surgical removal
Orbital cellulitis
- Periorbital redness and swelling often secondary to sinusitis
- Pathogens: S. pneumoniae, H. influenzae
- Fever, proptosis, periorbital swelling, opthalmoplegia, normal retinal exam
- Tx: nafcillin + ceftriaxone + metronidazole
Orbital fracture
- MC a/w blunt trauma to eye that produces orbital floor fracture
- Often a/w edema and ecchymoses of eyelids and periorbital region
- Vertical diplopia, prolapse of orbital contents into maxillary sinus, damage to infraorbital nerve
- Tx: varies w/ severity
Pterygium
- Raised, triangular encroachment of thickened conjunctiva on the nasal side of conjunctiva, may grow onto cornea
- D/t excessive exposure to wind, sun, sand
- Tx: surgical removal
Pinguecula
- Yellow-white conjunctival degeneration at the junction of the cornea and sclera on the temporal side of the conjunctiva
- Does NOT grow onto the cornea like pterygium does
- Usually doesn’t require tx
Optic neuritis
- Inflammation of optic nerve
- Causes: MS, methanol poisoning
- Blurry vision or loss of vision, may cause optic atrophy
- Tx: corticosteroids
Central retinal artery occlusion
Causes: embolization of plaque from ipsilateral carotid or opthalmic artery, giant cell temporal arteritis involving opthalmic artery
Sx: Sudden, painless, complete loss of vision in one eye, pallor of optic disk d/t narrowed arteries, “boxcar” segmentation of blood in retinal veins, cherry red macula
Tx: acetazolamide to lower intraocular pressure, carbogen, hyperbaric O2 therapy
Central retinal vein occlusion
- Causes: hypercoagulable state
Sx: Sudden painless unilateral loss of vision, swelling of optic disk, engorged retinal veins w/ hemorrhage
Tx: intravitreal injections, laser photocoagulation
Chronic open angle glaucoma
- Decreased rate of aqueous outflow into canal of Schlemm
- Common in persons with severe near-sightedness
- Bilateral aching eyes, pathologic cupping of the optic disks, night blindness and gradual loss of peripheral vision leading to tunnel vision and blindness
- Tx: 1st: Beta blockers, 2nd: prostaglandins, a-adrenergic agonists, pilocarpine, carbonic anhydrase inhibitors, laser trabeculoplasty
Acute closed angle glaucoma
- Narrowing of the anterior chamber angle
- Medical emergency
- Precipitated by mydriatic agent
- Uveitis, lens dislocation, severe pain a/w photophobia and blurry vision
- Red eye with steamy cornea (wut), pupil fixed and nonreactive to light
- Tx: pilocarpine + systemic carbonic anhydrase inhibitor to lower pressure to allow for laser surgery
Optic nerve atrophy
Pale optic disk
MC d/t optic neuritis or glaucoma
No effective treatment
Uveitis
- Inflammation of the uveal tract (iris, ciliary body, choroid)
- Causes: sarcoidosis, ulcerative colitis, ankylosing spondylitis
- Pain w/ blurry vision, miotic pupil, circumcorneal ciliary body vascular congestion, normal intraocular pressure, adhesions between iris and anterior lens capsule
- Tx: corticosteroids, atropine
Macular degeneration
- MCC permanent visual los in elderly
- Disruption of Bruch membrane in retina
- Dry: thinning of retina and formation of yellowish white deposits (drusen)
- Wet: extension of dry type, vessels under retina hemorrhage –> retinal cells die –> blind spots or distorted central vision
- Antioxidants may lower risk
- Tx: antiangiogenics, insertion of special lens
CMV retinitis
- MCC blindness in AIDS, usually when CD4 count
Cataracts
- Opacity in the lens
- Causes: advanced age, diabetes, infection
- Common in congenital infections
- Tx: cataract extraction
Malignant eye tumors
- Retinoblastoma in children
- Malignant melanoma
- Tx: enucleation
Meniere disease
- Increased endolymph in inner ear and loss of cochlear hairs
- Dizziness, vertigo, tinnitus, sensorineural hearing loss
- Tx: HCTZ + triamterene, surgery
Sensorineural defect
Weber test: lateralizes to normal ear
Conduction defect
Weber test: lateralizes to affected ear
- D/t degeneration of cochlear hairs
- Tx: amplification devices, cochlear implants
Otosclerosis
- MCC conduction deafness in elderly
- D/t fusion of ossicles
- Tx: amplification devices, surgery
Otitis media
- MCC conduction deafness in children
- Usually d/t Strep pneumoniae
- Tx: antipyrine and benzocaine drops for pain, controversy over use of abx
External otitis
- Inflammation of outer ear canal
- Swimmers ear –> tx: ear drops – polymixin B + neomycin + hydrocortisone + selenium sulfide shampoo
- Malignant external otitis: severe infection of outer ear canal in patients w/ diabetes, tx: imipenem-cilastatin
