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Astrocytes
o Star shaped glial cells in brain and spinal cord
o
Ependymal cells
o
Form the inner epithelial lining of cerebral ventricles and central canal of
spinal cord
Microglia
o
CNS phagocytes
Origin is mesodermal (all other CNS/PNS support cell types originate from
ectoderm)
Oligodendroglia
o Forms myelin around multiple CNS axons
o
These are the major types of glial cells found in white matter
Schwann Cells
o
Epineurium covers the entire nerve which consists of fascicles and blood vessels
Nerve structure
Nerve structure
2) Basement membrane
Glucose and amino acids cross BBB slowly and require carrier mediated transport
Hypothalamus
Hypothalamus
Frontal Lobe
o Primary motor cortex (4) and pre-motor cortex (6): responsible for
movement of muscles in contralateral half of body. Lesion results in
contralateral spastic hemiparesis.
o
Broca's area (44, 45): located in posterior part of the dominant frontal lobe,
specifically within the inferior frontal gyrus. Responsible for motor speech.
Parietal Lobe
o
Temporal Lobe
o
Wernickes area (22) superior temporal gyrus: lesion here results in sensory
(fluent/receptive) aphasia with poor comprehension
Occipital Lobe
o
Circle of Willis
Bitemporal hemianopsia
Circle of Willis
Spinal Cord
C1-C7 nerves: exit via intervertebral foramina at the level above the corresponding
vertebra
Spinal nerve C8 exits below vertebra C7. T1 through L5 exit at the level below the
corresponding vertebra.
The cauda equina consists of dorsal and ventral nerve roots of spinal nerves L2
coccygeal 1
o
Basal ganglia
Consists of the striatum, globus pallidus, subthalamic nuclei, and substantia nigra
o Corpus striatum = globus pallidus + putamen + caudate nucleus
o
Modulates thalamic outflow to the motor cortex (serves to plan and execute smooth
movements)
Many of the synaptic connections are inhibitory and use GABA (gamma
aminobutyric acid) as the inhibitory neurotransmitter
Lesion of striatum
o
Results in lead pipe rigidity, tremor, and reduced voluntary movement due to
destruction of dopaminergic neurons
Spinal tracts
Cranial Nerves
CN I (Olfactory)
o Mediates sense of smell (olfaction)
CN II (Optic)
o
CN III (Oculomotor)
o
Note:
Sphincter pupillae fibers are often first affected with:
1) Uncal (transtentorial) herniation
2) Aneurysms of the posterior communicating or carotid arteries
In contrast, diabetes mellitus diabetic CN III palsy, which spares the
sphincter pupillae and damages fibers located more centrally within the
nerve.
CN IV (Trochlear)
o
V1, V2 and V3 provide sensory innervation to the face and oral/nasal mucosa
lesion hemianesthesia
CN VI (Abducens)
o
CN VII (Facial)
o
The five motor branches of the facial nerve passing through the parotid gland are
(Use the mnemonic "To Zanzibar By Motor Car"):
o
Temporal
Zygomatic
Buccal
Marginal mandibular
Cervical
CN VIII (Vestibulocochlear)
o
CN IX (Glossopharyngeal)
o
Mediates taste and general sensation of the posterior 1/3rd tongue and
mucosa of the oropharynx. Also monitors input from carotid body and sinus
chemo-baroreceptors. The only pharyngeal muscle innervated by CN IX is
the stylopharyngeus.
Lesion causes loss of afferent limb of gag reflex and loss of taste and general
sensation from posterior third of tongue
CN X (Vagus)
o
CN XI (Accessory)
o
CN XI innervates 2 muscles:
1) sternocleidomastoid
2) trapezius
CN XII (Hypoglossal)
o
CN V sensory innervation
Spina bifida failure of posterior vertebral arches to close. Several forms which
include:
o
3) Spinal bifida occulta vertebral arches do not form in lumbar area but
spinal cord is normal. No symptoms, may have a lumbar dimple, lipoma, or
tuft of hair on exam.
TORCHeS infections:
o
Toxoplasma
Rubella
CMV
Herpes simplex, HIV
Syphilis (Treponema pallidum)
Arnold-Chiari malformation
o
Fetal alcohol syndrome: most common cause of mental retardation (affecting 1 4.8 per 1000 children born in the US) versus:
- Down syndrome: most common genetic cause of mental retardation
- Fragile X syndrome: most common inherited cause of mental retardation
o
Growth retardation
- small body size
- microcephaly
- midface hypoplasia
o
Midface abnormalities:
1) short palpebral fissures
2) epicanthal folds
3) long philtrum
4) thin upper lip
Heart defects:
- VSD (ventricular septal defect)
- ASD (atrial septal defect)
Meningomyelocele
OT OpTic gliomas
pheochromocytoma
Wilm's tumor
Retardation (mental)
Retinal lesions:
- mulberry tumors
- phakomas: round flat gray lesions located peripherally in the retina
Hamartomas
1) Neurologic deterioration
2) Facial port-wine stain nevus flammeus "birthmark" in the trigeminal nerve
distribution
3) Leptomeningeal hemangiomas
4) Buphthalmos (markedly enlarged eye) [1]
o
Children often suffer from visual disturbances (eg, hemianopia) and often
present with buphthalmos (markedly enlarged eye):
- Congenital glaucoma retained aqueous humor buphthalmos
(markedly enlarged eye)
Cerebrovascular Infarction
The middle cerebral artery and carotid bifurcations are the most common sites of
thrombotic occlusions
Alternatively, emboli can cause infarcts. The middle cerebral artery is the most
common site of embolic occlusion. Occlusion of the middle cerebral artery results
in contralateral paralysis, motor and sensory defects.
Lacunar strokes are pure motor (internal capsule) or pure sensory strokes (thalamus)
from obstruction of small vessels
Cerebrovascular Hemorrhages
Note:
Charcot-Bouchard aneurysms = microaneurysms that occur in the small
perforating arteries of the brainfor example:
- Lenticulostriate vessels (most common site)
- Thalamoperforator vessels
- Paramedian branches of the basilar artery
- Superior cerebellar arteries
- Anterior inferior cerebellar arteries
o
Most common sites of hypertensive bleeds in the CNS (in descending order
of frequency):
1) Basal ganglia is most common site50-60% of these basal ganglia
bleeds originate in the putamen
2) Thalamus
3) Pons
4) Cerebellum
General note:
Any increase in intracranial pressure is initially compensated by shifting of
cerebrospinal fluid into spinal subarachnoid space
Head injuries
Subdural hematoma:
o
hematomas are also more likely to cross suture lines than epidural
hematomas.
Add 2 quiz questions
Pyogenic meningitis can present with fever, headache, photophobia and nuchal
rigidity
o
Infective endocarditis
Bronchopulmonary infections
Viral infections
Slow progression viral infections: two types of viral CNS infection that have a slow
clinical progression
o
Infected during infancy but will not manifest with neurological symptoms
until early teenage years, usually fatal
Multiple Sclerosis
Epidemiology
o More common in women
o
Morphologic changes
o Confined to CNS
o
Clinical Manifestations
o
Variable course
Treatment:
o
-Interferon
Immunosuppressant therapy
Symptomatic treatment:
- Baclofen or other anti-spasmodics
- Pain management
Guillain-Barre syndrome
Autoimmune etiology
Clinical manifestation
Most patients survive but severe cases can have respiratory failure with
death
Hallmark
o
Increased CSF protein concentration with only modest increase in cell count.
Treatment
o
Plasmapheresis
Alzheimer's disease
Clinical findings
o Slow, progressive intellectual deterioration
o
Etiology
o
Neurofibrillary tangles
Heavy metal toxicity can cause cognitive impairment, often with peripheral
neuropathy. Wilson's disease is an important genetic disorder resulting in heavy
metal toxicity with neurological impairment. The treatment for heavy metal toxicity
is chelation therapy.
Dementia with Lewy bodies is a form of dementia that presents with fluctuating
dementia, parkinsonism, and visual hallucinations. It is associated with Alzheimer's
disease, and often patients have pathological changes of both diseases.
o
Lewy bodies are found in the cerebral cortex and the substantia nigra.
Huntington disease
Etiology
o Autosomal dominant
o
Clinical manifestations
o
Parkinson disease
Etiology
o Loss of the neurons in the substantia nigra (revealed grossly in the
depigmentation of the SN in brain stem section) dopaminergic ouput
from the SNPC to the basal ganglia.
Dopamine acts on 2 receptors in the basal ganglia circuit:
D1: excitatoryactivation of this receptor in movement
D2: inhibitoryactivation of this receptor causes disinhibition of the
thalamus motion
It follows that loss of DA to the basal ganglia causes output to the motor
system bradykinesia.
Clinical manifestations
o
Shuffling of gait
Drugs and toxins, especially dopamine antagonists, MPTP (1-methyl-4phenyl-1,2,3,6-tetrahydropyridine, an illegal street drug)
Treatment
o
L-dopa/Carbidopa: converted to dopamine in the CNS. Unlike dopamine, Ldopa can cross blood brain barrier. Carbidopa is a peripheral decarboxylase
inhibitor that increases the bioavailability of L-dopa to the brain
Selegiline: selective MAO type B inhibitor that prevents dopamine
breakdown
Benztropine: antimuscarinic that improves tremor and rigidity
Etiology
o Degeneration of upper AND lower motor neurons
o
Clinical manifestations
o Symmetric atrophy, fasciculation of muscles (lower motor neuron signs)
o
Treatment options:
- Mostly supportive care (pain control, intubation by tracheostomy)
- Riluzole (which blocks glutamatergic neurotransmission by inhibiting glutamate
release and inactivating voltage-gated Na channels) is an FDA-approved medication
that extends survival and/or time to tracheostomy.
Brain Tumors
The most common brain tumors are metastatic (from a primary outside of the brain)
Glioblastoma Multiforme (grade 4 astrocytoma):
o
Histopathology:
1. Marked anaplasia (nuclear atypia, pleomorphism) with florid vascular
endothelial hyperplasia secondary to VEGF
2. Pseudopalisading necrosisareas of necrosis and hemorrhage
surrounded by rows of malignant cells
Meningioma:
o
Medulloblastoma:
o
Can occur at any age, but 75% are found in children (median age 9)
Neuroblastoma: [1]
o
Neuroblastomas are most often found in adrenal medulla but can be found
anywhere along the sympathetic chain
Retinoblastoma:
Schwannoma:
o
Oligodendroglioma:
o
Cerebral location
Astrocytoma:
o
Schwannoma
Seizures
Seizures may be partial (affects one area of the brain) or generalized (diffuse)
However, partial seizures may progress to be generalized
Myoclonic seizures
o
Status epilepticus
o
Anti-seizure drugs
Phenytoin
o Increases Na channel inactivation
o
Is a Class IB antiarrhythmic
Side effects:
- Neuro S/Sx: diplopia, nystagmus, ataxia
- Gingival hyperplasia
- Hirsutism
- SLE-like syndrome (ie, drug-induced lupus)
- folate absorption folate deficiency megaloblastic anemia
- vitamin D absorption vitamin D deficiency osteomalacia
[1]
Carbamazepine
o Increases Na channel inactivation
o
First line agent for tonic-clonic seizures (as is phenytoin) ; first line agent for
trigeminal neuralgia
Side effects/toxicities:
- Hematologic S/Sx: agranulocytosis, aplastic anemia
- Stevens-Johnson syndrome
- SIADH dilutional hyponatremia
- vitamin D absorption vitamin D deficiency osteomalacia
- Teratogenic effects: spina bifida, cleft lip/palate
[2] [3] [4]
Gabapentin
o Increases GABA (inhibitory neurotransmitter) release indirectly by acting on
N-type Ca channels.
o
Ethosuximide
o
Side effects:
- Stevens-Johnson syndrome
- urticaria
- GI symptoms, fatigue, headache
Lamotrigine
o
Topiramate
o
Valproic Acid
o
Opioid analgesics
Clinical usage:
o
Toxicity
o
Respiratory depression
Addiction
Treatment of toxicity
o
Sumatriptan
Dantrolene
Calcium binds to troponin C, and this causes troponin I to release its hold on
actin. Tropomyosin can then move away from the binding groove, and
myosin heads can bind to actin filament.
Used to treat:
o
Note: other vasodilators such as nitroglycerin and calcium channel blockers will
increase ICP by increased cerebral blood volume from vasodilatation of cerebral
blood vessels. Beware of using these agents in situations of increased ICP such as
head bleed