Gianani intro to neuropathology Flashcards
Approach to the patient with neurologic disease
- primary or secondary?
Most patients in hospital with a coma have a metabolic, toxic or infectious cause
Approach to the patient with neurologic disease- time course of disease
Vascular pathology: seconds to minutes
Abscesses: hours to days
Neoplasms: weeks to months
Degenerative disease: months (e.g. prion disease) to years (e.g. Huntington chorea) to decades (e.g. Alzheimer and Parkinson disease)
Multiple sclerosis: relapses and remissions over months to years
Mnemonic for toxic/metabolic causes of neurological diseases:
DEENO (drugs, endocrine, electrolytes, nutritional, organ failure)
localizing findings: cerebrum
decreased mental status seizures motor/ sensory abnormalities of the head visual field defects movement abnormalities (e.g. tremor, chorea)
localizing findings: brainstem
cranial nerve defects
“crossed” defect (i.e. head and limbs deffects on opposite sides)
localizing findings: spinal cord
back pain
specific body level/ sparing of the head
sphincter dysfunction
localizing findings: spinal roots
radiating limb pain
pattern of loss
areflexia
localizing findings: peripheral nerves
distal limb distribution
nerve distribution of abnormality
“stocking and glove” pattern
areflexia
localizing findings: neuromuscular junction
bilateral weakness increasing with exertion
proximal limb symptoms
sparing of sensation
localizing findings: muscle
bilateral weakness
sparing of sensation
Localization: Focal, multifocal or diffuse
Mass lesions (e.g. abscesses, bleeds, and neoplasms) typically have localized symptoms
Acute, diffuse, symmetrical symptoms are typically viral, metabolic or toxic in origin
localization: presence of pain
Only the meninges and vessels have pain fibers
Pathophysiologic pattern
Neuronal diseases
(i.e. gray matter) typically have cognitive loss, movement disorders or seizures
Pathophysiologic pattern: White matter
typically has “long tract” findings (i.e. motor, sensory, visual or cerebellar)
Pathophysiologic pattern: Progressive, symmetric loss is usually
metabolic or degenerative
Dementia
(loss of mental power) is a generic term, not a disease entity. Any pathology that causes significant brain damage, at any age, can cause dementia. The causes of dementia include:
- Stroke and ischemic encephalopathy (multi-infarct or vascular dementia)
- Hippocampal sclerosis
- Head trauma (subdural hematomas, diffuse axonal injury, chronic traumatic encephalopathy)
- Hydrocephalus
- CNS infections (HIV encephalitis, Creutzfeldt-Jakob disease)
- Metabolic CNS disorders (lysosomal storage and peroxisomal diseases)
- Demyelinative diseases (multiple sclerosis)
- Neurodegenerative diseases (Alzheimer’s disease, Parkinson’s disease, diffuse Lewy body dementia, Huntington’s disease, and other)
- Neuropsychiatric disorders
- Severe medical illness or organ failure
- The effects of medications
Three imaging modalities are commonly used in clinical practice:
CT scan, MRI scan, and angiography
CT scans are preferred in
Emergencies (fast)
Trauma (evaluation of skull fractures)
Stroke (sensitive for fresh hemorrhage)
CT scan
X-rays measure the density of a tissue.
Hypodense: Air is black (e.g. sinuses of skull), fat appears near black (e.g. subcutis of scalp) and water appears dark gray (e.g. CSF)
Isodense: white matter, with more fat from myelin, is darker than gray matter.
Hyperdense: ** bone is white, as is fresh blood. As fibrinolysis occurs, the clot becomes isodense with brain at 1 week, and hypodense by weeks 2-3 (the density of the clot can be used to date the time of the bleed).
Blood Can Be Very Bad.
This stands for B - blood C - cisterns B - brain V - ventricles B - bones
Basic categories of blood in the brain
epidural, subdural, intraparenchymal /intracerebral, intraventricular, and subarachnoid.
subdural hemorrhage
crescent shaped, does cross suture lines
epidural hemorrhage
lens shaped, does not cross suture lines
Intraparenchymal / intracerbral hemorrhage
high density bleeds most often in the basal ganglia area if due to HTN
Subarachnoid hemorrhage
due most often to aneurysms, CT sensitivity decreases sharply with time
Cisterns on CT
any opening in the subarachnoid space of the brain created by a separation of the arachnoid and pia mater.
4 key cisterns (Circummesencephalic, Suprasellar, Quadrigeminal and Sylvian)
2 Key questions to answer regarding the 4 key cisterns
Is there blood?
-Are the cisterns open?
Examine the *brain * on CT for
Symmetry - make sure sulci and gyri appear the same on both sides. (easiest when patient not rotated in the scanner)
Grey-white differentiation - the earliest sign of a CVA on CT scan is the loss of the grey-white interface on CT scan. Compare side to side.
Shift - the falx should be in the midline with ventricles the same on both sides. Check for effacement of sulci (unilateral or bilateral).
Hyper/ hypodenisty - blood, calcification and IV contrast are hyperdense (appear lighter) and air, fat and areas of tumor ischemia are hypodense (appear darker).
the earliest sign of a CVA on CT scan is
the loss of the grey-white interface on CT scan. Compare side to side.
Ventricles (on CT)
Examine for IIIrd, IVth and lateral ventricles for dilation or compression/shift.
Pathologic processes cause dilation (hydrocephalus) or compression/shift. Communicating vs. Non-communicating. Communicating hydrocephalus is first evident in dilation of the temporal horns (normally small, slit-like). The lateral, IIIrd, and IVth ventricles need to be examined for effacement, shift, and blood.
Bone on CT
has the highest density on CT scan (whitest in appearance.) Evaluate for fracture.
Ring-enhancing lesion
seen with any localizing mass
abscess (e.g. bacterial toxoplasma)
glioblastoma
metastasis
MRI scan
Uses magnetism to measure proton properties of chemicals in cells. Brightness, referred to as “intensity” of signal, is basically determined by water versus fat content.
T1-weighted images look like CT scans. In T2-weighted images, water is bright, so that edema, gliosis and gray matter are prominent, making most pathology easier to see than on T1 images. T2 images have bright CSF and therefore FLAIR technique is used to make CSF dark. FLAIR MRI images are the most sensitive for small, subtle abnormalities.
Doppler ultrasound
is used to measure vessel lumen diameter and blood flow of the carotid arteries.
Spiral CT angiography
requires intravenous injection of contrast material to obtain images of blood vessels. It is used as a supplement to MRA
Magnetic resonance angiography (MRA)
typically uses gadolinium to enhance contrast of blood flow. This is the current method of choice to detect vessel narrowing, thrombosis and dissection. It is a sensitive technique for carotid stenosis, aneurysms and malformations.
Neuropil
a broad term defined as any area in the nervous system composed of mostly unmyelinated axons, dendrites and glial cell processes that forms a synaptically dense region containing a relatively low number of cell bodies. The most prevalent anatomical region of neuropil is the brain
= unmyelinated neuronal axons
oligodendrocytes and Schwann cells - inflammatory reactions
Oligodendrocytes undergo inflammatory reaction in MS patients
Schwann cells undergo inflammatory reaction in Guillain Barre syndrome patients
Neocortex layers (6)
MGP GPM-nemonic
» Molecular » external Granular » external Pyramidal » internal Granular » internal Pyramidal » Multiform
Cerebral cortex – three parts:
Archicortex – connects limbic system to the cortex
» Paleocortex – linked to olfactory system
» Neocortex – 90% of the cortex
Chromatolysis
Chromatolysis…caused by the axon being severed
If the axon is transsected, the RER disaggregates and the neuronal body balloons. The cytoplasm becomes smooth and the nucleus is displaced toward the periphery of the cell. This appearance, which is called central chromatolysis, is a reversible change that develops during repair of a neuron that has been disconnected from its target.
Neuronal injury and death
Hypoxia, ischemia, and hypoglycemia cause irreversible neuronal injury. Injured neurons shrink, become eosinophilic due to condensation of mitochondria, and their nuclei become pyknotic. Such neurons are referred to as anoxic neurons.
In Alzheimer’s disease
abnormal filaments (paired helical filaments) appear in the perikaryon, forming neurofibrillary tangles (NFTs).
Astrocytes
- staining
Glial fibrillary acidic protein stains astrocytes
astrocytes– enlargement
in hepatic encephalopathy. In acute metabolic disorders such as hepatic encephalopathy, hyperammonemia, and cerebral ischemia, astrocytes enlarge. Their nuclei are large and appear clear in H&E stains.
Neurons can survive
only 5-10 minutes of hypoxia/ischemia before irreversible injury. Light microscopic evidence of death is evident in 12-24 hours as “red neurons”.
Gliosis
Chronic or degenerative neuronal death results in cell loss. This is typically recognized by the reactive glial changes (“gliosis”).
Gliosis is the most important histopathologic indicator of chronic CNS injury.
- Characterized by astrocyte hyperplasia and hypertrophy
- Astrocytes contain glial fibrillary acidic protein (GFAP), used to identify them.
Cellular pathology of the CNS
Neurons of different types and different locations have unique functions and needs. They may show selective vulnerability to a given disease process even when they are in different anatomical location. Some injuries, such as trauma and ischemia, damage all of the neurons in a given anatomical location, resulting in a characteristic clinical pattern of disease.
Microglial cells
are CNS macrophages and are present in inflammatory foci
