Neuro 2 Flashcards
Cerebrovascular disease
Brain injury hemorrhagic ischemic
Ischemia
Reduced perfusion
Loss of ATP and membrane potential for electrical activity
Increased cytoplasmic Ca-cytotoxic
Excitotoxicity-inappropriate release of excitatory aa
Glutamate-ca through NMDA cytotoxic
Penumbra
Area of at risk tissue at region of transition between necrotic tissue and normal brain
- rescued with anti apoptotic
- ischemia may cause apoptosis
Are embolisms or thrombosis more common
Embolism
Global cerebral ischemia (diffuse ischemic/hypoxic encephalopathy)
Generalized decrease renal perfusion
Can be minor or severe
What causes global cerebral ischemia
Cardiac arrest, shock, severe hypertension
What cells are most sensitive to global cerebral ischemia
Neurons , glial
Pyramidal cells of hippocampus CA1 sommer
Cerebellar purkinje and neocortex bets
Pseudolaminar necrosis
Band like pattern cells remain next to meninges
Due to some cells being more sensitive
Symptoms of global cerebral ischemia
Total loss of brain function
Patients who survive often are in persistent vegetative state brain dead and brainstem damage
When left on respirator with undergo respirator brain-autolytic processs with gradual liquefaction
Border zone (watershed) infarcts
Distal brain or spine or arterial supply, the border between arterial territories
What border zone is most vulnerable to infarct
Between ACA(legs and dick) and MCA (convexities)
Linear para sagittal infarction
Area of cortex is most at risk and will show a sickle shaped band of necrosis over the cerebral convexities a few cm lateral to the interhemispheric fissure
Why are areas in watershed areas between ACA and MCA most vulnerable
Large pyramidal neurons in particular are most sensitive to hypoxic and hypoglycemic stress
When are border zone watershed infarcts seen
Hypotensive episodes
Morphology of global ischemia
Edema and swollen brain wide gyri narrow sulci
Ongoing liquefication necrosis
Demarcation bt white and grey
12-24 hours-red neuron
2 weeks-necrosis, macrophages, vascular proliferation, gliosis
After-macrophages, remove necrotic tissue, loss of architecture, gliosis
Pseudolaminar necrosis-neuronal loss and gliosis uneven in cortec some layers preserved some not
Fibroblast proliferation rare
Focal cerebral ischemia
Reduction or cessation or blood flow to localized area
Sustained get infarction
Damage depends on collateral
Where is there no collateral circulation
Deeper areas and white matter
Thalamus, basal ganglia, deep white
Embolism
From cardiac mural thrombi
plaque in ICA go to MCA
Where do most embolism events occur
Gray white junction where narrowing and acute branching of the vessels trap emboli
MCA location
Supplies convexities of cortec arms and feet on homunculus
What artery is most frequently affected by embolism infarction
ICA send to MCA
Shower embolism(like fat emboli after bone break)
Generalized cerebral dysfunction with higher cortical function disturbance and consciousness
Widespread white matter hemorrhages -characteristic of embolization of bone marrow after trauma
Thrombotic occlusion
Usually from atherosclerosis and plaque rupture
Most common sites of thrombotic occlusions
Carotid bifurcation, origin of MCA and either end of basilar artery
Thrombi
Progressive narrowing may cause fragmentation
Thrombosis of intracranial artery
Infarction , which can be hemorrhagic, but the hemorrhage typically does not extend into subarachnoid or subdural locations-stays confined to intraparenchymal
What may also cause luminal narrowing
Vasculitis
Infections vasculitis
TB, syphilis, opportunistic CMV and aspergillos
Polyarteritis nodosa
Non infectious vasculitis may involve cerebral vessels and cause infarcts in brain
Primary angiitis
Granulomatous angiitis of nervous system
Inflammation affects many small to medium parenchymal and subarachnoid vessels
Chronic inflammation, multinucleated giant cells, and destruction of the vessel wall
Patients develop a diffuse encephalitic of multifocal clinical picture with cognitive dysfunction
Patients improve with steroid and immunosuppressive treatment
What are the two types of infarcts
Hemorrhagic and non hemorrhagic
Hemorrhagic infarcts
When emboli partially occlude a vessel or undergo dissolution
Nonhemorrhagic infarcts
More likely to arise from thrombosis over atherosclerotic lesions
Infarcts are typically ___ in the beginning because infarcts are the result of a loss of blood
Nonhemorrhagic
With repercussion injury from collaterals or from breakdown of the clot the infarct can becomes __
Hemorrhagic
The hemorrhagic infarcts are typically petechial and can be multiple of confluent management.treatment differs greatly as __ __ is contraindicated in hemorrhagic infarcts
Thrombocytic therapy
Brain swelling with infarcts
No
Non hemorrhagic infarct morphology
Little change in first 6 hrs From edges inward 12 h-red neurons edema Loss of tissueendothelial and glial cells begin to swell and myelination falls Neutrophils
48 hrspale doft and swollen corticomedullary junction indistinct
Macrophages and microglia are now the dominant cell type and will be 2-3 weeks persist
2-10 days brain becomes gelatinous and friable more distinct demarcation infarct and non..reactive astrocytes
Months-astrocytes response stops and leaves glial fiber meshwork mixed with capillaries and perivascular CT
PIA AND ARACHNOID MATER ARE UNAFFECTED AND DO NOT CONTRIBUTE TO THE HEALING PROCESS
Hemorrhagic infarct morphology
Same as hemorrhagic but there is blood extravasation and resorption
Prob if anti coagulant -thrombolytic therapy tPA contraindicated in hemorrhagic infarct
Venous infarcts are often hemorrhagic and can occur after thrombotic occlusion of the superior sagittal sinus or occlusion of other cerebral veins
Spinal cord infarction
With hypoperfusion or result of traumatic interruption of the feeding tributaries derived from the aorta
Rarely can be due to occlusion of the anterior spinal artery as the result of embolism or vasculitis
Effects of hypertension cerebrovasculardisease
Lacunae infarcts, slit hemorrhages, and hypertensive encephalopathy as well as massive hypertensive intracerebral hemorrhage
Lacunar infarcts/occlusion
Hypertension affects deep penetrating arteries and arterioles that supply the basal ganglia and hemispheric white matter and brainstem,. These cerebral vessels develop arteriolar sclerosis and can become occluded -associated with widening of perivascular spaces without tissue infarction
What can lacunar infarcts lead to
Single or multiple small cavityary infarcts known as lacunas (less than 12 mm wide)
Where do lacuna occur
Lenticular nucleus, thalamus, internal capsule, deep white matter, caudate nucleus, pons
Etat crible
Lacunar vessels associated with widening or perivascular spaces without tissueinfarction
Slit hemorrhages
HTN can cause rupture of small caliber penetrating vessels and the development of small hemorrhage
Hemorrhage will be resorted and leave small slit like cavity that is surrounded by a brownish discoloration
There is focal tissue destruction, pigment laden macrophages and gliosis
Hypertensive encephalopathy
From malignant HTN from eye and kidney problems
Diffuse cerebral dysfunction (headache, confusion, vomiting, convulsions, and coma_
Edema and herniation of tonsil or transtentorial
Petechial and fibrinoid necrosis of arterioles in grey and white matter
Vascular dementia
From bilateral grey (cortex, thalamus, basal ganglia) and white matter (centrum semiovale) infarcts over many months and years
Clinical vascular dementia
Dementia, gait, pseudobulbar signs, neuro deficits
Causes of vascular dementia
Cerebral atherosclerosis, vessel thrombosis or embolus, arterial sclerosis
Biswanger disease
Pattern of injury preferentially involves large areas of the subcortical white matter with myelin and axon loss. Usually large areas of subcortical white matter with myelin and axon loss
What hemorrhages are associated with trauma
Epidural and subdural
Subarachnoid and intraparenchymal hemorrhages
Underlying cerebrovascular disease
IntraParenchymal hemorrhage
Rupture small vessels with sudden onset of symptoms
Peak 60
Ganglionic hemorrhage
In basal ganglia and thalamus from hypertension
Lobar hemorrhage
In cerebral hemisphere from CAA
What is risk factor of deep brain parenchymal hemorrhages
HTN
Where are hemorrhages associated with HTN
Deep white/grey matter followed by brainstem and cerebellum
Duret hemorrhage
Pontine , putamen, thalamus, pons
Acute hemorrhage
Extravasion of blood with a subsequent compression of surrounding parenchyma
Old hemorrhage
Cavitary lesion with a rim of brown (slit hemorrhage) but initially they consist of a central core of clotted blood with a rim of brain tissue with anoxic and glial changes with edema
After intraparenchymal hemorrhage
Hemosiderein and lipid laden macrophages and reactive astrocytes along periphery
CAA
Lobar hemorrhage
AB40 which weakens walls leading to hemorrhage
Microbleeds
NO FIBROSIS vessels rigid
Only affects leptomeningeal and cerebral cortical arterioles
Amyloid, dense uniform deposits@@@
Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy CADSIL
AD
NOTCH3 causes misfolding of receptor protein on vascular smooth
Recurrent strokes and dementiafirst seen in white matter around 35 and infarcts 45-50
Concentric thickening of media adventitia
Loss of smooth muscle
Basophils PAs deposits that appear as osmiphilic compact granular material
Clinical CADAIL
Devastating if affects large brain portions
Granular resolution after of hematoma its improvement
Saccular aneurysm
At birth congenital defect cause dilation later
Subarachnoid hemorrhage
Base of brain less likely to cause mass effect
Most common intracranial aneurysm
Berry
Where is berry
Anterior circulation near arterial branch point
Structural problem with berry
Absence of smooth muscle or intimate elastic lamina at birth
Are berry congenital prob
No smooth muscle deficit is congenital aneurysm are acquired after
Berry media
Ok
Risk factor saccular berry
Genetic
AD polycystic kidney disease, helpers danlos, neurofibromatosis type I, Maryam, smoking HTN
Where does rupture of berry aneurysm happen
Apex of aneurysm leads to extravasation of blood into subarachnoid space, substance of the brain or both
The wall next to a berry aneurysm has intimacy thickening and attenuation of the media
Ok
Why get non communicating hydrocephalus after berry aneurysm
Organization of the subarachnoid hemorrhage occluding foramina of luschka and magendie
Risk of saccular aneurysm
Organs and stool HTN, female,
Clinical presentation saccular berry
Worst headache of life thunderclap headache
Subarachnoid
Then vasospasm in basal subarachnoid hemorrhages that involve major vessels in circle of Willis
Heal-obstruction of csf flow
Arteriovenous malformations
In cerebral hemispheres of a young adult
Subarachnoid space or brain
Tangled vessels that show prominent, pulsatile arteriovenous shunting with high blood slow-bypass a capillary bed
Can be respected
Separated by gliotic tissue with evidence of prior hemorrhage
Some vessels show duplication and fragmentation of the internal elastic lamina while others show marked thickening or partial replacement of the media by hyalinized CT
Cavernous malformations
Distended loosely organized vascular channels back to back with collagenized walls of variable thickness
No. Brain parenchyma between vessels
In cerebellum, pons, and subcortical regions
Low flow channels that do not participate in AV shunting
There is commonly evidence of prior hemorrhage, infarct or calcification
Familial AD
Capillary telangiectasias
Microscopic foci of dilated thin walled vessels separated by normal parenchyma
In pons
Venous angiomas
Aggregates of ecstatic venous channels
Foix alajouanine disease (angiodysgenetic necrotizint myelopathy)
Venous angiomatous malformation of the spinal cord and overlying meninges
Most common in the lumbosacral region
Associated with ischemic injury to the spinal cord and slowly progressive neurological symptoms
AVM
Males
10-20 seizure disorder, intracerebral hemorrhage, or subarachnoid hemorrhage
Most common site is the MCA (hands face), espicially posterior branches
Can lead to CHF
Stroke
Acute onset of neurological deficits resulting from hemorrhagic or obstructive vascular lesion
What are the two most common causes of the spontaneous subarachnoid hemorrhage
Aneurysm or arteriovenous malformation
Infection:four principal routes by which microbes enter the nervous system
Hematogenous (venous also sinus)
Meningitis :arachnoid and pia caused by microbes
Meningoencephalitis
Chemical meningitis
Acute progenitor meningitis
Neutrophilils, elevated protein, reduced glucose
Aseptic meningitis poliomyelitis
Lymphocytic, moderately elevated, normal glucose
Chemical (sterile ) meningitis
Neutrophilis elevated protein
Normal glucose
Brain abscess, subdural empyema
Elevated WBC, elevated protein normal glucose
TB meningitis
Mixed mononuclear cells and neutrophilis cells
Elevated protein
Normal reduced glucose
Arthropod borne viral encephalitis
Neutrophilis then rapidly lymphocytic
Elevated protein
Normal glucose
Bacterial
Increased neutrophils increased protein decreased glucose
Increased pressure
Viral
Increased lymphocytes increased protein normal glucose
Increased pressure
Fungal and mycobacterium
Increased lymphocytes increased protein decreased glucose
Increased pressure
Acute progenitor meningitis
Bacterial
Aseptic meningitis
Acute or subacute viral
Chronic meningitis
TB, spirochetal, cryptococcal
Meningoencephalitis
Inflammation of meninges and brain parenchyma
Chemical meningitis
Non bacterial irritate into subarachnoid space causes inflammation of meninges
Chemo
Neonates acute progenitor meningitis
Group b strep (agalactiae)
Adolescent acute progenitor meningitis
Neisseria meningitidis college
Elderly acute progenitor meningitis
Strep pneumonia and listeria monocytogenes
Most common organism to cause acute progenitor meningitis
Strep pneumo
Immune suppressed people acute progenitor meningitis
Klebsiella or anaerobic organisms
Will have uncharacteristic CSF findings
Haemophilus influenza and meningitis
Immunization now infants don’t get
Clinical presentation of meningitis
Headache, photophobia, cloudy consciousness, stiff neck
Bacterial cultured
Waterhouse friderichsen syndrome
Meningitis associated with septicemia with hemorrhagic infarction rothe adrenal glands and cutaneous petechial
Occurs with meningococcal and pneumococcal meningitis
Acute aseptic meningitis
Less fulminant than progenitor
Self limited
Enterovirus
Morphology bacterial meningitis
Exudate in leptomeninges (pia and arachnoid)
H. Influenza-basal distribution
Pneumococcal-cerebral and sagittal sinus distribution
Neutrophils in leptomeningeal vessels (less severe) or subarachnoid space (severe)
Fulminant mengitis
Inflammatory cells infiltrate the walls of the leptomeningeal veins ad can cause cerebritis
Phlebitis
Lead to venous thrombosis and hemorrhagic infarction of the underlying brain
Leptomeningeal fibrosis can happen after progenitor meningitis and lead to hydrocephalus
The capsular polysaccharide of the microbe can make a gelatinous exudate that promotes arachnoid fibrosis known as chronic adhesive arachnoiditis
Chronic adhesive arachnoiditis
No CSF flow
Bacterial meningitis lead to CSF what
Obstruction at foramina luschka and magendie making communications hydrocephalus
Brain abscesses
Localized focus of necrosis of brain tissue with inflammation that is usually caused by bacteria
RING enhancesmtn on CT scans
What are ring enhancements of brain abscesses
As abscess organized it is ringed by fibroblasts that deposit collagen -characteristic of an abscess in the CNS
Describe ring enhancement
Granulation tissue with fibrosis is a typical healing inflammatory response reaction to a cerebral abscess, usually caused by bacterial organisms. Collagen deposition ground a ring enhancing lesion is typical for an abscess that organizes. The ring enhancement results from increased vascularity from capillary proliferation and disrupted BBB. A common source for such brain abscess is a lung infection
Primary infiltrate of brain abscess
Neutrophils
What are brain abscesses associated with
Fever
Where are brain abscesses commonly located
Cerebral hemispheres away from the ventricular system
What causes brain abscess
Direct implantation of microbe , local extension of the microbes from adjacent foci, or hematogenous spread from a primary site like the heart, lungs, extremity bones, or tooth extraction
Predisposing conditions for brain abscesses
Acute bacterial endocarditis :lead to many abscess
Congenital heart disease with right to left shunting and loss of pulmonary filtration chronic pulmonary sepsis like bronchiectasis
Immune suppression
Most common bacteria for brain abscess
Strep and staph
Brain abscess morphology
Central liquefaction necrosis
Leaky vasogenic edema
Clinical presentation brain abscess
Progressive focal neuro deficit
ICP signs
CSF high white count and increased protein but glucose normal
When is glucose decreased in csf
Bacterial
Complications of brain abscess
Rupture with ventriculitis or meningitis and venous sinus thrombosis .=
Cubdural empyema
Bacterial or fungal infections of the skull bones or air sinuses can spread to the subdural space to produce a subdural empyema
Are arachnoid and subarachnoid affected in subdural empyema
No
Venous occlusion subdural empyema
Mass effect of thrombophlebitis of bridging veins that cross the subdural space and infarction
Clinical presentation subdural empyema
Fever, headache, stiff neck
Csf with white cell, increased protein, normal glucose
If leave subdural empyema untreated
Focal neuro signs and symptoms , lethargy, coma
Treat subdural empyema
Residuum and thickened dura
Extramural abscess
Associated with osteomyelitis
Comes from another source of infection from surgery or sinus
Can cause spinal cord compression if occur in spinal epidural space
Cause of bacterial meningoencephalitis
TB, syphilis borrelia species
TB meningitis
Headache, malaise, mental confusion, vomit
CSF pleocytosis of mononuclear cells, elevated protein, normal to moderate reduction of glucose
Complication of TB meningitis
Arachnoid fibrosis producing hydrocephalus and obliterating endarteritis producing arterial occlusion and infarction of the brain
Nerve roots
Granulomas cause space occupying lesion and symptoms
Morphology TB meningitis
TB acid fast
Obliterating endarteritis and marked intimacy thickening
Tuberculomas
Well circumscribed intraparenchymal mass
Caseous necrosis in mussel
Calcification in inactive
Mass space occupying lesion
Tertiary syphilis
Mix of tabes dorsalis, paretic neurosyphilis, meningovascular neurosyphilis
Taboparesis
Neurosyphilis and aids
Increase
Meningovascular neurosyphilis
Chronic involves base of the brain and cerebral convexities and spinal leptomeninges
What is meningovascular neurosyphilis associated with
Obliterating endarteritis (heubner arteritis) accompanied by perivascular inflammmatiory reaction rich in plasma cells and lymphocytes
Cerebral Gemma’s
Paretic neurosyphilis
Treponema
Mood changes
General paresis of the insane
Iron deposits demonstrable by Prussian blue stain
Tables dorsalis
Damage dorsal column
Widen gait
Poor proprioception and locomotor ataxia
Charcot joints-loss of pain leading to skin and joint damage
Lightening Pain and loss of DTR
Pallor and atrophy in the dorsal columns of spinal cord
Neuroborreliosis
From ticks Lyme disease
Aseptic meningitis, facial nerve palsies, and encephalopathy
Arthropod borne viral encephalitis
Arboviruses tropical regions
Seizures, confusion, ocular palsies, reflex assymmetry
Morphology viral meningoencephalitis
Perivascular lymphocytes
Foci of necrosis in grey and white
Single cell neuronal necrosis with phagocytosis of the debris neurophagis
Microglial nodules
West nile
Polio type encephalitis
Herpes encephalitis
TLR4 defect Mood memory behavior Temporal lobe Hemorrhagic lesions of temporal lobes Necrotizing infection
Hsv2
Meningitis can pass to kids
HIV-hemorrhage and necrotizing encephalopathy
Varicella zoster
Chicken pox
Kid come back as shingles
Adult -granulomatous arteritis
Immunocompromised-acute encephalopathy characterized by numerous sharply circumscribed demyelinating lesions that undergo necrosis
CMV
Microcephalic
Periventricular leukomalacis
Poliomyelitis
Tropism for anterior horn
Perivascular cuffs, neuronophagia of anterior horn motor neurons of the spinal cord
Neuronophagia of the anterior horn motor neurons of the spinal cord
Affected anterior horns of the spinal cord LMN and atrophy of msucles
Polio features
LMN-areflexia, atrophy, Antonia, flaccid paralysis
UMN-hyperreflexia, hypertonic, spastic paralysis
Polio and diaphragm
Death
Destroy motor neurons
Paresis/paralysis
Post polio syndrome
Progressive weakness and decreased muscle mass in affected area
Rabies
Pyramidal neurons of the hippocampus and purkinje cells of cerebellum
Nehru
Symptoms rabies
Local paresthesia around wound
Conjunction fo thes symptoms with local paresthesia around the wound is nearly diagnostic
HIV
Acute-lymphocytic meningitis, perivascular inflammation, and some myelin
Immune reconstitution inflammation syndrome
Paradoxical deterioration after starting therapy from the exuberant reconstituted immune system
HIV encephalopathy
Chronic inflammation axonal swelling
PML
JC polyomavirus
Oligodendrocytes demyelination is its principle pathological effect in immune compromised
Glassy amp Philip viral inclusions
Clinical PML
Focal and relentlessly progressive neuro signs
Image -extensive multifocal lesions in hemispheric or cerebellar white matter
Subacute sclerosis’s penencephalitis
Kids or young adults months or years after initial measles virus
SSPE clinic
Progressice cognitive decline , limb spacisitiy and seizures
Widespread gliosis
Lots of viral inclusions that are mostly found in the nuclei of oligodendrocytes and neurons
Fungal meningoencephalitis
Immunocompromised
Aspergillus, cryptococcal neoforms
-histoplasma capsulatum, coccidiodes immitis and blastomyces dermatitidis can affect cns after an initial pulmonary or cutaneous infection
Most fungi et into brain how
Hematogenous
What are 3 forms of CNS fungal injury
Chronic meningitis, vasculitis, parenchymal invasion
Vasculitis
Mucormycosis, aspergilosis after infect
Love to invade blood cells
Parenchymal nfection
Granulomas or abscesses
Candida or cryptococcal
Candidiasis causes multiple microabsceses with or without granulomas
Cryptococcal meningitis
AIDS fulminant and fatal 2 weeks or indolent
Protein CSF and yeast
Cryptococcal meningitis morphology
Obstruct outflow of CSF from the foramina or luschka and magendie leading to hydrocephalus
Soap bubbles-small cysts within parenchyma espicially the basal ganglia parenchymal lesions consist of aggregates of organisms within perivascular virchow node
INDIA PINK CYSTS
Cerebral toxoplasmosis
Opportunistic
HIV
Ring enhancing lesion
Pregnancy-TORCH
Cerebral toxoplasmosis morphology
Affect cerebral cortex and deep grey nuclei
Necrosis, hemorrhage, chronic inflammation, macrophage infiltration and vascular proliferation
Cerebral amebiasis
Naegleria or acanthamoeba
PAS meth silver
Immunofluoresence sulture and olecular methods
Cerebral malaria
Rapidly progressing encephalopathy
Complication of infection by plasmodium falciparum with highest mortality rate
Most likely vascular dysfunction
Reduced cerebral blood flow, ataxia, seizures, coma, cognitive deficits
Prions
Sporadic 90%
PrP
Polymorphism at 127 M or V homozygous overrepresent CJD
Heterozygous 129
Protective
Morphology prions
Spongiform change caused by intracellular cavuoles in neurons and glial cells and progressive dementia
PrPsc
Proteinase k resistant in tissue
CJD
Rapidly progressive dementia
Gerstmann straussler scheinker syndrome
Progressive cerebellar ataxi
CJD
Familiar
70s
Iatrogenic (corneal transplant, brain electrodes, contaminated Growth hormone)
Clinical CJD
Subtle changes in memory and behavior followed by rapidl dementia and smartly myoclonus (pronounced involuntary jerking muscle contractions on sudden stimulation’s
Survival CJD
7 months
VCJD
Exposure to bovine spongiform encephalopathy from contaminated food or blood transfusion
Young adults
Behavior change
Extensive cortical plaques surround halo of spongiform change
Limited to 129 MET MET homozygous
CJD morphology
Cyst like spaces (status spongiosus)
Spongiform transformation of cerebral cortec and deep gray
Uneven formations of small and empty microscopic vacuoles within neuropil and perilaryon of neurons
Kuru plaques Congo red and PAs positive in cerebellum
Fatal familial insomnia
Sleep disturbances in initial stages
Specific mutation in PRNP gene
What mutation in FFI PRNP gene
Substitution for aspargine at residue 178 of PrPsc result in FFI when is occurs in a PRNP allele encoding methionine at codon 129 but causes CJD when present in tande, with Celine at this spot
Asparagine at 178 and M at 129
FFI
Asparagina at 178 and valine at 129
CJD
FFI clinical
3 years
Then develop ataxia, autonomic disturbances, stupor, and coma
Spongiform pathology inFFI
No
Characterized by neuronal loss and reactive gliosis in anterior ventral and dorsomedial nuclei of the thalamus instead
Neuronal loss also prominent in inferior olivary nuclei
