Pathology Flashcards
Immunologic destruction of normal myelin
Etiology unknown
Hereditary – HLA types A3, B7, Dw2, DRw2, DRw4, DRw6; common in Nordic Caucasians
Viruses – abnormal immune response to measles virus, retroviral (HTLV-1) demyelination
Epidemiology
Most common 20-40 years
Females > males
Gross pathology
Plaques at multiple CNS sites-Around lateral ventricles, optic nerves/chiasm/tracts, corpus callosum, cerebellar peduncles, cerebellum, spinal cord
Microscopic pathology
Loss of myelin (seen on LFB stain) with relative preservation of axons (silver or Bielschowsky stain)
Plaques centered around or extend along blood vessels (venules) with perivascular lymphocytes and plasma cells
Lipid laden macrophages filled with myelin fragments and breakdown products
Reactive astrocytosis
Clinical presentation
Multiple episodes of relapse and remission
Multiple CNS sites effected (visual, motor, sensory, cerebellar, brainstem related symptoms)
Stresses precipitate exacerbations
MRI is the most sensitive technique for lesion detection
Demyelinating foci are hyperintense on T2 weighted image
Natural history
Long course of alternating relapses and remission with increasing functional limitations
Eventual death from intercurrent infection, respiratory compromise, pulmonary embolus
Acute form with involvement of vital brainstem centers is fatal at first presentation
multiple sclerosis (MS)
Acute fulminating immunologic destruction of myelin days/weeks after immune challenge
Often follows respiratory infection
Vaccination (rabies, smallpox)
Infection (measles, rubella, mumps, influenza, pertussis, strep) - precipitating infection is cleared before onset
Most common in children and adolescents
Monophasic but may relapse
Acute onset with hemiplegia, ataxia, optic neuritis and sometimes seizures
Demyelinating lesions centered around venules with perivascular chronic inflammation and macrophages
Multifocal (asymmetric) MRI hyperintense foci within white matter
Most cases are non-fatal with rapid recovery but a small subset can have residual neurologic deficit or die in acute phase
Acute Disseminated Encephalomyelitis (ADEM)
Defective enzyme in metabolic pathway related to neurolipids, carbohydrates, amino acids, nucleic acids, pigments, or metals
Non-catabolized metabolite accumulates and destroys neurons and/or glia
Rare diseases of infancy and childhood
Motor disturbances, seizures, deafness, blindness, retardation
Insidious onset, relentlessly progressive
Primary Encephalopathies
Primary leukodystrophy
Diffuse bilaterally symmetric white matter degeneration
Canavan Disease
CNS metabolism perturbed by extra-CNS disease
Metabolic substrate deprivation (oxygen, glucose)
Metabolic cofactor deficiency (vitamins, hormones)
Major organ failure (heart, lungs, kidney, liver)
Chemical imbalances (fluid, electrolytes, acid-base, calcium, osmolality)
Intoxications (drugs, poisons, hormones)
Miscellaneous (sepsis, temperature extremes, trauma)
Seen in any age group
Acute/subacute onset
Amenable to treatment
Secondary Encephalopathies
Clinical expression of cerebral thrombosis, embolism, or hemorrhage
Event lasts less than 24 hours
Transient Ischemic Attach (TIA)
Vascular event in CNS with sudden onset and effects lasting more than 24 hours
Fifth most common cause of death in the US, incidence and prevalence is declining
Major risk factors: Hypertension, Cardiac disease, Cigarette smoking, Hyperlipidemia, Diabetes mellitus
Other risk factors: Oral contraceptives, Hematologic disease, Thrombotic coagulopathies, Vasculitis, Cerebral amyloid angiopathy, Dissecting aneurysm in extracranial blood vessel, Cocaine, heroin, amphetamines
Stroke
Normal blood flow but reduced O2 content
Low environmental partial pressure of oxygen
Acute respiratory failure
Carbon monoxide poisoning
Most hypoxic conditions depress cardiac output leading to cerebral ischemia
Hypoxia
O2 content of blood is normal but blood flow is reduced
Cardiac arrest
Hypovolemic shock
More damaging than hypoxia, toxic metabolic wastes accumulate
Ischemia
Characteristic of thrombotic infarcts
No reperfusion to necrotic area
Anemic cerebral infarct
Characteristic of embolic infarcts
Reperfusion of necrotic area leads to extravasation of blood from necrotic vessels
Hemorrhagic cerebral infarct
0-2 days after infarct
subtle tissue softening, dusky grey matter discoloration, blurring of grey/white matter demarcation
red neurons – neuronal cytoplasm shrinks and turns pink, nucleus collapses and breaks up
neutrophils migrate from vessels at infarct edge
Acute infarct
2-4 days after infarct
findings of acute stage are more pronounced
swelling (edema) of tissue within mass effect
red neurons break up (liquefactive necrosis) and disappear
neutrophils are replaced by lymphocytes and macrophages
Subacute infarct
4+ days after infarct
early liquefactive necrosis and late cystic cavitation (no fibrous scar formation)
cavity replaces liquefied dead tissue, spanned by reactive astrocytic processes and capillaries
reactive gliosis and partial tissue damage in surrounding non-necrotic parenchyma with neuronal encrustation (iron/calcium salt deposits on neurons in infarct rim)
Chronic infarct
chronic hypertension results in hyaline arteriolosclerosis and lipohyalinosis in deep perforating central branches
vessel walls become thicker but less elastic, lumen narrows and microaneurysms may develop
thrombosis leads to lacunar infarcts, small cavities in the brain located in the basal ganglia, thalamus, pons, or deep cerebellum
vessel rupture leads to intracerebral hemorrhage
hypertensive hemorrhage
thrombosis of dural venous sinus or cortical vein usually due to infection, tumor invasion, or thrombotic diathesis
blocked venous drainage leads to congestion, ischemia, hemorrhagic necrosis in drainage territory
cerebral venous thrombosis
trauma
skull fracture lacerates underlying dural artery (most often the middle meningeal)
blood under arterial pressure accumulates in potential space between skull and dura
hematoma mass effect may cause herniation
patient may experience lucid interval between injury and neurologic deterioration
medical emergency requiring prompt evacuation
epidural hemorrhage
trauma
tear in bridging vein between cortical surfaces and dural sinus
cortical vein attached to brain
bridging vein tethered in dura
inertial movement of brain relative to skull/dura shears bridging vein
venous blood accumulates between dura and arachnoid
organized by dural fibroblasts that form membranes around the hematoma
granulation tissue capillaries of organizing hematoma may rupture with minor trauma (re-bleed)
subdural hemorrhage
trauma, saccular aneurysm, AVM rupture, spread of intraventricular or intracerebral hemorrhage
parenchymal contusion or lacerations bleeding through disrupted pia or ependyma
basilar blood vessels ruptured by basilar skull fracture
dissecting aneurysm of vertebral arteries
subarachnoid hemorrhage
Associated with connective tissue disease, cerebral vascular malformations, aortic coarctation, AD PCKD, neurofibromatosis 1, smoking, HTN, turbulent blood flow
most common in the anterior circle of Willis
rupture occurs at the dome and extravasated blood collects in the subarachnoid space, brain parenchyma and ventricular system
rupture can result in severe headache, loss of consciousness and death
rupture might result in circle of Willis vasospasm resulting in infarct or arachnoid fibrosis which causes communicating hydrocephalus
saccular (berry) aneurysms
trauma, chronic hypertension, hemorrhagic infarct, cerebral amyloid angiopathy
results from contusions and lacerations
intracerebral/parenchymal hemorrhage
extension of intracerebral hemorrhage that ruptures ventricular lining
intraventricular hemorrhage
amyloid deposited in small and medium-sized cortical and leptomeningeal vessels resulting in thickened but weakened vessels that are subject to rupture (see apple green birefringence on congo red stain)
cerebral hemorrhage is more superficial
reflects involvement of leptomeningeal and superficial cortical vessels, may see several hemorrhages of different ages in different brain areas
affected vessels have double-barrel appearance
cerebral amyloid angiopathy and intracerebral hemorrhage
malformation of cerebral blood vessels
intracerebral +/- subarachnoid hemorrhage, seizure disorder
most often involves MCA
tortuous large caliber vascular tangle in parenchyma +/- subarachnoid space
rapid flow rates
direct AV shunt with no capillary bed, involves arterioles, veins and arteriolized veins
brain tissue is seen between abnormal vessels
reactive changes are seen in the surrounding brain (hemosiderin, Ca2+, gliosis)
arteriovenous malformation (AVM)
malformation of cerebral blood vessels
intracerebral with or without subarachnoid hemorrhage, seizure disorder
occurs most often in the brainstem, cerebellum, and cerebral subcortical white matter
grossly resembles hematoma
sluggish flow rates
abnormal vessels with thin fibrous wall, without intervening brain tissue
no smooth muscle, elastic
cavernous hemangioma (cavernoma)
loss of memory and other cognitive abilities secondary to cerebrovascular disease
multi-infarct dementia
bilateral infarcts destroying threshold volume of grey matter or functionally critical grey matter (thalamus, hippocampus)
diffuse white matter disease
arteriolosclerosis leads to myelin damage, axonal loss, disconnection of association areas
subcortical arteriolosclerosis leukoencephalopathy
associated with chronic HTN, diabetes, cerebral atherosclerosis
vascular dementia
parenchymal bruise from impact of brain with skull
head is struck, brain develops inertia relative to the skull resulting in impact between brain and skull, brain may rebound against inner skull opposite to the impact site
contusion
parenchymal contusion at impact site
associated with blows to stationary head and falls
tissue and vascular damage with hemorrhage
impact greatest on crowns of gyri
follows organization sequence of intracerebral hemorrhage
coup injury
parenchymal contusion opposite to the impact site due to rebound injury
associated with falls
tissue and vascular damage with hemorrhage
impact greatest on crowns of gyri
follows organization sequence of intracerebral hemorrhage
countercoup injury
stretching and shearing of axons in deep white matter (corpus callosum, periventricular white matter, brainstem)
may be seen with open or closed head injury
patients are unconscious from the moment of injury without a lucid interval (remain unconscious, vegetative, or disabled until death)
axons severed at nodes of Ranvier, axoplasmic flow disrupted, rounded axonal swellings
small hemorrhages in the corpus callosum, dorsal midbrain, dorsal pons with or without contusions or lacerations
rounded swellings in white matter neuropil on microscopy, no axons on Bielschowsky stain
diffuse axonal injury (DAI)
Occurs in malnourished patients, especially alcoholics
Wernicke’e encephalopathy/Korsakoff’s syndrome
Bilateral hemorrhage and necrosis in mammillary bodies and periventricular grey matter
Peripheral neuropathy
Heart failure
Thiamine (B1) Deficiency
Occurs in malnourished and pernicious anemia patients
Interferes with hematopoiesis and CNS myelin production leading to megaloblastic anemia and myelin destruction in posterior and lateral columns of spinal cord (subacute combined degeneration)
Cobalamin (B12) Deficiency
Elevated ammonia levels
Toxic to CNS metabolism
Neuronal membrane depolarization and neuronal hyperexcitability
Perturbed neurotransmitter metabolism and imbalance among neurotransmitters
Alzheimer type 2 astrocyte
Grey matter astrocytes with swollen clear nuclei and no visible cytoplasm
Hepatic Encephalopathy
Cerebral cortical necrosis (layers 3 and 5 or cortex)
Neuronal necrosis in hippocampus (CA1 region), Purkinje cells of cerebellum
Necrosis in watershed zones of major vascular territories
hypoxia/hypoglycemia
Patient with abnormal serum Na+ corrected too rapidly (alcoholics, chronically ill)
Diamond-shaped area of myelin destruction in central pons
Central pontine myelinolysis
non-infectious inflammation due to chemical irritation in the subarachnoid space
keratin from ruptured intracranial epidermoid cyst (misplaced squamous epithelium trapped inside developing skull during fetal development) can cause inflammation
chemical meningitis
spread of metastatic cancer/lymphoma in the subarachnoid space
meningeal lymphomatosis
carcinomatous/lymphomatous meningitis
leptomeninges infected by bacteria that induce pus formation
neonates: GBS, Gram negatives, L. monocytogenes, S. aureus
children: S. pneumoniae, H. influenzae type B (if not immunized), N. meningitidis
adults: S. pneumoniae (all ages, sporadic), N. menigitidis (young adults, crowded living conditions), Gram negative rods, L. monocytogenes, S. aureua
fever, chills, anorexia, vomiting
headache, photophobia, irritability, decreased level of consciousness, stiff neck
septicemia Waterhouse-Friedrichsen syndrome (adrenal septic hemorrhagic necrosis, skin petechiae, systemic collapse)
neurologic impairment at presentation
CSF findings Increased opening pressure Increase CSF cells (mostly PMNs) Increase CSF protein Decrease CSF glucose
Pus accumulates in the subarachnoid space (obscures view of underlying brain surface)
Pus may collect at the base of the brain
Subarachnoid space filled with PMNs
May see inflammation +/- thrombosis of blood vessels passing through subarachnoid space
acute pyogenic meningitis
Meningitis caused by viral infection
No organism found on Gram stain of culture of CSF
Enteroviruses – poliovirus, echovirus, coxsackievirus; HIVl HSV, mumps, measles
Less fulminant presentation than acute pyogenic meningitis
Spontaneous remission
CSF findings Normal or increased opening pressure Increased cells (lymphocytes) Increased protein Normal glucose Negative microscopy
acute aseptic meningitis
Localized pus-forming infection of brain parenchyma
Multiple sources of infection
Hematogenous (cardiac, pulmonary)
Local extension (oro-sino-naso-facial)
Immunocompetent patient: staph and strep species
Immunocompromised patient: Toxoplasma gondii, Nocardia asteroids, L. monocytogenes, gram negative bacteria, mycobacteria, fungi
Clinical presentation
Variable: indolent to fulminant
Fever, headache, focal neurologic deficit, seizures
CSF findings – lumbar puncture rarely indicated and contraindicated with increased ICP Increased opening pressure Increased cells (PMNs and lymphocytes) Increased protein Normal glucose Negative cultures
Diagnosed by imaging and biopsy cultures
Potentially fatal without treatment (surgery and antibiotics)
Complications
Rupture into ventricle or subarachnoid space
Dural venous sinus thrombosis
Early cerebritis (1-3 weeks) – hyperemic softened focus Developed purulent abscess – suppurative cavity with fibrous capsule and surrounding edema; often at grey-white junction
Central core of suppurative liquefactive necrosis
Intermediate zone of proliferating granulation tissue
Outer ring of gliotic edematous brain
brain abscess
Pus-forming infection between inner dural surface and arachnoid
Spread of skull or sinus infection
Organized fibroblast from dura
Thrombophlebitis of dural venous sinus or bridging veins with cerebral venous thrombosis
subdural emypema
Pus forming infection between bone and outer dural surface
Spread from osteomyelitis or sinusitis
Spinal infection may compress cord and require emergency decompression/drainage
epidural abscess
Chronic granulomatous meningitis = basilar infection resulting in adhesive arachnoiditis (fibrosis) that traps basilar vessels and cranial nerves
Tuberculoma = brain abscess with caseous necrosis surrounded by granulomatous inflammation
Tuberculous spondylitis/Pott’s disease = vertebral destruction, spinal deformity, epidural abscess
Immunocompetent: M. tuberculosis
Immunocompromised: M. avium-intracellulare
CSF findings Increased cells (lymphocytes) Increased protein Normal or slightly decreased glucose AFB positive
CNS Mycobacterium infection
Treponema pallidum may spread to meninges
Early CNS infection is limited to meninges
Asymptomatic: normal to increased cells (lymphocytes), protein, normal glucose, + CSF VLDR
Symptomatic: presents as acute aseptic meningitis
Late CNS infection:
Involvement may be limited to meninges and arteries (mesoderm) - Meningeal gummas, Fibrosing vascular infection occluding lumens (obliterative endarteritis) with plasma cells resulting in parenchymal infarcts
Involvement may include meninges, arteries, and parenchyma - Neuronal loss, microglial activation (rod cells), gliosis, Progressive mental deterioration resulting in dementia, Tabes dorsalis = degeneration of spinal dorsal columns (ataxia, loss of pain sensation)
Gumma
Granulomatous tissue reaction
Necrosis with preservation of tissue reticulin
Prominent plasma cells
Occurs in meninges and may extend into the brain cortex
May occur in brain parenchyma in late disease
Neurosyphilis
CNS infection by spirochete Borrelia burgdorferi transmitted by Ixodes ticks
Part of a multisystem disorder involving skin, cardiovascular, joint, PNS, and CNS systems
Aseptic meningitis, CN VII palsy, peripheral neuropathy, encephalopathy
Microglial activation (rod cells), granulomas, vasculitis
Neuroborreliosis
Viral infection of meninges and brain parenchyma
Perivascular and parenchymal mononuclear cell infiltrates
Perivascular lymphocytic cuffing
Microglial nodules (lymphocytes, plasma cells, macrophages, rod cells) Microglial cell activation Microglia nuclei enlarge, long, and thin (rod cells)
Neuronal death and phagocytosis, often in a microglial nodule (neuronophagia)
Gliosis
Viral inclusions may be present
May be followed by demyelinating syndrome (ADEM)
viral meningoencephalitis
Sporadic viral encephalitis
Primary infection (lips, face) or reactivation from trigeminal ganglion
Targets medial temporal lobe, limbic regions
Causes necrotizing, hemorrhagic infection
Intranuclear viral inclusions in neurons and glia
CNS HSV1 infection
Adults
Retrograde spread to CNS from sacral dorsal root ganglia, latency established after genital infection
Aseptic meningitis in healthy adults
Necrotizing encephalitis in the immunocompromised
Neonates
Acquired during birth or transplacentally
Necrotizing encephalitis
CNS HSV2 infection
Childhood viral exanthema
Varicella latency established in DRG and trigeminal ganglia, reactivation with anterograde axonal transport to skin in dermatomal distribution
Herpes zoster by primary infection or reactivation may travel retrograde to spinal cord/brain especially in the immunosuppressed
Myeloradiculitis, encephalitis, CNS vascular infection
Intranuclear inclusions in neurons and glia
CNS Varicella Zoster Virus infection
Intrauterine infection
Targets periventricular regions with severe necrosis leading to periventricular calcification, microcephaly, and CNS malformations
Infection in immunosuppressed leads to encephalitis, retinitis, myeloradiculitis
Cellular enlargement with prominent intranuclear inclusions in neurons, glia, endothelial cells
CNS Cytomeglovirus infection
Epidemic viral encephalitis
Viruses endemic in birds and small mammals, transmitted by arthropods (mosquitoes, ticks)
Mostly seen in summer and early fall
Eastern Equine Encephalitis, West Nile Virus
CNS Arbovirus infection
Enterovirus that infects gut and spreads to blood
Some strains can invade CNS from blood and produce aseptic meningitis +/- acute myelitis
In myelitis, virus targets motor neurons in anterior horn of spinal cord and brainstem resulting in flaccid areflexic paralysis and respiratory muscle involvement which may be fatal
Vaccination has reduced worldwide incidence
CNS poliovirus infection
Virus endemic in small mammals
Virus transmitted to humans via bite of infected animal, travels retrograde via PNS axons to CNS (time to onset of disease reflects bite distance from CNS)
Fulminant encephalitis: neuronal cytoplasmic inclusions that are round and pink and are seen best in Purkinje cells and hippocampal pyramidal neurons
CNS Rabies infection
Rare complication of early age measles infection
Non-productive (no viral replication) CNS latency of altered measles virus after primary infection
Onset of progressive behavior, cognitive, and motor disturbances months to years after infection
Encephalitis with widespread neuronal and white matter destruction
Intranuclear inclusion in neurons and oligodendrocytes
Subacute sclerosing panencephalitis (SSPE)
Reactivation during a period of immunocompromised of latent JC polyomavirus infection acquired earlier in life
Primary JC virus infection is asymptomatic, latency in lymphocytes and kidney
JC virus infects glia on reactivation
Oligodendrocyte involvement leads to myelin loss
Astrocyte involvement leads to enlarged bizarre astrocyte nuclei
Progressive neurologic syndrome due to CNS white matter destruction
Multiple foci of secondary demyelination in cerebral, cerebellar, brainstem white matter
Viral intranuclear inclusion in oligodendrocyte nuclei
progressive multifocal leukoencephalopathy (PML)
Early/with seroconversion: aseptic meningitis
Late: subacute meningoencephalitis
Direct HIV infection of cerebral microglia and macrophages
Neurons destroyed by cytokines, BBB failure
Clinical dementia, motor disturbances, seizures
More common in pediatric patients
Secondary infectious and malignant CNS complications
CNS HIV infection
Target host endothelium, reproduce in host cells
Spread by insect vectors (ticks, lice, mites)
Infect CNS vascular endothelium resulting in vasculitis, hemorrhage, thrombosis, infarction
CNS Rickettsial infection
Infection of meninges +/- parenchyma associated with immunocompromised
Causative agents: candida albicans, aspergillus fumigatus, mucor, Cryptococcus neoformans
Inflammatory response may be granulomatous or minimal depending on host status and infecting agent
fungal meningoencephalitis
Meningocerebral infection by Toxoplasma gondii
Cat is the definitive host, humans infected via contaminated oocyst containing cat feces
Cysts ingested, tachyzoites infect GI macrophages and are disseminated via blood and lymph
Intrauterine/neonatal
Transplacental passage of tachyzoites during primary maternal infection
Fetal meningoencephalitis
targets subpial and subventricular regions
widespread grey and white matter destruction
diffuse brain calcification, hydrocephalus, CNS malformations
primary/reactivation in immunocompromised
ring enhancing cerebral abscess(es) at grey/white cortical function or deep grey matter
meningitis, vasculitis, retinitis
free tachyzoites and encysted bradyzoites on microscopy
CNS Toxoplasmosis
Larvae of Tenia solium encyst in human CNS following ingestion of eggs in undercooked pork
Humans are dead end intermediate hosts
Neurocysticercosis
Neuronal protein PrPc converted from alpha helix to beta pleated sheet PrPsc
PrPsc is resistant to cellular degradation mechanisms and normal techniques of sterilization and tissue fixation
Aberrant PrPsc may arise spontaneously, be inherited, or introduced via surgery, ingestion, or organ transplantation
Sporadic prion disease
Creutzfeldt-Jacob disease
Rapidly progressive dementia with myoclonic jerks
Fatal in less than 1 year
Widespread neuronal loss, gliosis, spongiform change in grey matter (no inflammatory reponse)
Heritable prion disease
Gerstmann-Straussler-Scheinker syndrome
Fatal familial insomnia
Infectious prion disease
Kuru – transmission via cannibalism
Transmissible Spongiform Encephalopathies
Autosomal dominant disorder resulting from CAG repeat on chromosome 4 huntintin gene
Loss of neurons in caudate, putamen, thalamus, and cerebral cortex
Extrapyramidal movement disorder +/- dementia
Huntington’s Chorea
Autosomal recessive disorder resulting from GAA repeat on chromosome 9 frataxin gene
Loss of axons/neurons in spinal cord, cerebellum (spinocerebellar degeneration)
Gait ataxia, cerebellar/posterior column/pyramidal tract signs and symptoms
Friedreich’s ataxia
Autosomal dominant, segmental repeat in PMP 22 gene for myelin structural protein, chromosome 17
Myelin damage and axonal loss in peripheral nerves
Distal leg weakness and muscle atrophy +/- sensory loss
Peroneal muscular atrophy/hereditary and sensory neuropathy type 1/Charcot-Marie-Tooth disease
X-linked recessive deletion in dystrophin gene
Slowly progressive wasting of skeletal and cardiac muscle
Progressive loss of muscle function, immobility, respiratory paralysis
Duchenne’s Muscular Dystrophy
Most common dementia
Widespread neuronal loss and gliosis
Cerebral cortex, brainstem, basal ganglia
Decrease in brain weight and volume
Increase in ventricular volume (hydrocephalus ex vacuo)
Senile/neuritic plaques
Extracellular, amyloid core, neurites with abnormal cytoskeletal filaments (tau protein)
Neurofibrillary tangles
Intraneuronal, altered cytoskeletal elements (tau protein)
Granulovacuolar degeneration
Lysosomes with altered cytoskeletal proteins (tau)
Hirano bodies
Abnormal cytoskeletal microfilaments (actin)
Amyloid angiopathy
Deposition of amyloid in blood vessels of leptomeninges, cerebral cortex
Neuronal loss leads to decreased neurotransmitters
Decreased ACh in cerebral cortex and nucleus basalic of Maynert
NE, DA, somatostatin, 5-hydroxytriptamine, substance P may decrease
Genetic predisposition
Chromosomes 21, 14, 1, 19 implicated
Early onset in Down’s syndrome (trisomy 21)
Alzheimer’s Disease
Dementing illness clinically similar to Alzheimer’s but involving mostly frontal lobe related symptoms
Marked atrophy of the frontal lobe and anterior portion of the superior temporal gyrus
Microscopic round silver-positive neuronal inclusions (pick bodies)
Pick’s disease
Cumulative consequence of many small strokes (multi-infarct dementia)
Diffuse damage to CNS white matter from arteriolar disease (hypertension) – Binswanger encephalopathy
Vascular Dementia
Intermittent increases in CSF pressure enlarge ventricles
Dementia, gait ataxia, urinary incontinence
Normal Pressure Hydrocephalus
Extrapyramidal movement disorder due to loss of pigmented neurons in substantia nigra
Bradykinesia, cogwheel rigidity, resting tremor
Pallor of substantia nigra and locus ceruleus
Round pink target-like inclusions (Lewy bodies) in surviving neurons of the substantia nigra and locus ceruleus
Idiopathic Parkinson’s Disease
Primary motor neuron disease
Idiopathic fetal and infantile degeneration of lower motor neurons (spinal cord, cranial nerve nuclei) without corticospinal tract signs
SMA type 1 (Werdig-Hoffman disease) – fatal cause of neonatal hypotonia, autosomal recessive disease (chromosome 5)
Loss of motor neurons in anterior horn of spinal cord
Atrophy of anterior spinal nerve roots and skeletal muscle
Spinal Muscular Atrophy
Primary motor neuron disease
Loss of motor neurons and astrocytes in spinal cord, brainstem, and motor cortex
Upper and lower motor neuron signs
Degeneration of corticospinal tract
Amyotrophic Lateral Sclerosis
Secondary motor neuron disease
Lytic infection of the motor neurons caused by enterovirus
Can be confined to spinal cord but may also affect the brain
In chronic case, asymmetric loss of anterior horn motor neurons and muscle atrophy
Lower extremities are involved more often than trunk or upper extremities
Poliomyelitis motor neuron disease
