IUHS Student-2-Student USMLE Step 1 Recall
Central Nervous System
Developmental Defects/Brain Injury
Subfalcine (cingulate gyrus) herniation
this occurs when unilateral or asymmetric expansion of the cerebral hemisphere displaces the cingulate gyrus under the falx cerebri...
this is often associated with compression of branches of the anterior cerebral artery...
Transtentorial (uncal, mesial temporal) herniation
occur when the medial aspect of the temporal lobe is compressed against the free margin of the tentorium cerebelli...
as displacement of the temporal lobe extends, the third cranial nerve is compressed, resulting in pupillary dilation and impairment of ocular movements on the side of the lesion...
the posterior cerebral artery is also often compressed, resulting in ischemic injury to the terrritory supplied by that vessel, including the primary visual cortex...
progression of transtentorial herniation is often accompanied by hemorrhagic lesions in the midbrain and pons, termed secondary brain stem, or Duret, hemorrhages...
these linear or flame shaped lesions usually occur in the midline and paramedian regions...
Hydrocephalus
presents
as episodes of vomiting, headaches, problems with
acquisition of motor skills, cranial nerve dysfunction, and problems breathing...
hydrocephalus refers to the accumulation of excessive CSF within the ventricular system of the brain...
most such cases occur as a consequence of decreased resorption of CSF, although in rare instances (tumors of the choroid plexus), overproduction of CSF may be responsible...
whatever it origin, an increase in CSF within the ventricles expands them and causes an elevation in intracranial pressure...
if hydrocephalus dev elops before closure of the cranial sutures, there is enlargement of the head, manifested by an increase in head circumference...hydrocephalus developing after fusion of the sutures, in contrast, is associated with expansion of the ventricles and increased intracranial pressure, without a change in head circumference...
hydrocephalus often results from congenital aqueductal stenosis where there is impaired circulation of CSF due to narrowing of the cerebral aqueduct connecting 3rd and 4th ventricles...
Anencephaly
results from failure of the anterior rostral neuropore to close during the 4th week...
this condition is incompatible with life as only in atrophic, dysfunction brain forms...
occurs in 1/1000 births; may be associated with polyhydramnios and rachischisis...with improper formation of rostral end of the brain, the fetus lacks the neural mechanism for swallowing and cannot reduce the amount of amniotic fluid in the amniotic sac...
folate intake during pregnancy prevents anencephaly, spina bifida and other neural tube defects...
all that remains in its place is the area cerebrovasculosa, a flattened remnant of disorganized brain tissue with admixed ependyma, chorid plexus, and meningothelia cells...
Anencephaly is a congenital form of adrenal hypoplasia, whereas corticosteroid therapy leads to the acquired form of hypoplasia (atrophy).
this defect can be seen at 17 weeks gestation...
Encephalocele
encephalocele
is a diverticulum of malformed CNS tissue extending
through a defect in the cranium...
it most often occurs in the occipital region or in the posterior fossa...
This is a form of neural tube defect in which the occiput is not formed and herniation of brain occurs. Alpha fetoprotein is increased in amniotic fluid or maternal serum.
Myelomeningoceles
myelomeningocele (or meningomyelocele) refers to extension of CNS tissue through a defect in the vertebral column; the term meningocele applies when there is only a meningeal extrusion...
clinical neurologic dysfunction is most often related to the structural abnormality of the cord itself and to superimposed infection that extends from the thin, overlying skin...
myelomeningoceles occur most commonly in the lumbocacral region, and the patient manifests clinical deficits referable to motor and sensory function in the lower extremities as well as disturbacnes of bowel and bladder control...
increased alpha fetal protein...
Polymicrogyria
characerized by a loss of the normal external contour of the convolutions, which on macroscopic examination appear small, unusually numerous, and irregularly formed...
the gray matter is composed of four layers (or fewer), with entrapment of apparent meningeal tissue at points of fusion of what would otherwise be the cortical surface....
25 human genetic syndromes have been recognized to be associated with malformations of cortical development, including polymicrogyria...
Microcephaly
small brain and skull with normal-sized face resulting in severe mental retardation...
can occur in a wide range of clincial settings, including chromosome abnormalities, fetal alcohol syndrome, and human immunodeficiency virus 1 (HIV-1) infection acquired in utero...
a reduction in the number of neurons that reach the neocortex is postulated, and this leads to a simplification of the gyral folding...
this can range from a noticeable decrease in the number of gyris to total absence, leaving a smooth-surfaced brain, lissencephaly (agyria)...
Holoprosencephaly
failure of midline cleavage of the forebrain resulting in a single ventricle as the cerebral vesicles do not properly form...
associated with the absence of the olfactory bulbs and tracts...
may be seen in newborn with Trisomy 13 (patau syndrome) and fetal alcholol syndrome...
associated with a monoventricle...
mutations in the sonic hedgehog gene (a member of a family of secreted proteins synthesized by the notochord and neural plate during induction) have been shown in some cases of holoprosencephaly...
Arnold-Chiari Malformation
malformation
of the cerebellum and brainstem in which brainstem
descends posteriorly through foramen magnum; this condition causes
hydrocephalus...
associated with lumbar myelomeningocele in half of the cases...
other associated changes include caudal displacement of the medulla, malformation of the tectum, aqueductal stenosis, cerebral heterotopias, and hydromyelia...
in Chiari I malformation, low-lying cerebellar tonsils extend down the vertebral canal and may cause symptoms referable to obstruction of CSF flow and medullary compression that are amenable to neurosurgical intervention...
Dandy-Walker Malformation
characterized by enlarged posterior fossa...the cerebellar vermis is absent or present only in rudimentary form in its anterior portion...
in its place is a large midline cyst that is lined by ependyma and is contigous with leptomeninges on its outer surface...
this cyst represents the expanded, roofless fourth ventricle in the absence of a normally formed vermis...
dysplasias of brain stem nuclei are commonly found in association with Dandy-Walker malformation...
Syringomyelia and Hydromyelia
characterized
by a discontinuous multisegmental or confluent expansion of the
ependyma lined central canal of the cord (hydromyelia)
or by the formation of fluid-filled cleftlike
cavity in the inner poriton of the cord (syringomyelia, syrinx)...
these lesions are associated with destruction of the adjacent gray and white matter and are surrounded by a dense feltwork of reactive gliosis...
the cervical cord is most often affected, and the slitlike cavity may extend into the brain stem (syringobulbia)...associated anomalies of the spinal column are common (verteral fusions, scoliosis, platybasia)...
as many as 90% of cases of syringomyelia have the Chiari I malformation; a minority are associated with intraspinal tumors or follow traumatic injury...
in general, the histologic appearance of the lesions is comparable...the disease generally becomes manifest in the second or third decade of life...
bilateral loss of pain and temperature sensations in the hands at the level of the lesion...
the distinctive initial clinical symptoms and signs of a syrinx are progressive evolution of dissociated sensory loss of pain and temperature sensation in the upper extremities, retention of position sense, and absence of motor deficits due to early involvement of the crossing anterior spinal commissural fibers...
Cerebral Palsy
refers to a non-progressive neurologic motor deficit characterized by spasticity, dystonia, ataxia/athetosis, and paresis attributable to insults occuring during the prenatal and perinatal periods...
signs and symptoms may be inapparent at birth and only later declare themselves as development occurs...
postmortem examination of children with this syndrome has shown a wide range of neuropathologic findings, including hemorrhages and infarctions...
Concussion
concussion is a clinical syndrome of alteration of consciousness secondary to head injury typically brought about by a change in the momentum of the head (movement of the head arrested by a rigid surface)...
the characteristic neurologic picture includes instantaneous onset of transient neurologic dysfunction, including loss of consciousness, temporary respiratory arrest, and loss of reflexes...
although neurologic recovery is complete, amnesia for the event persists, and many postconcussive neuropsychiatric syndromes have been described...
the pathogenesis of the sudden disruption of nervous activity is unknown; but biochemical and physiologic abnormalities occur, such as depolarization due to excitatory amino acid - mediated ionic fluxes across cell membranes, depletion of mitochondrial adenosine triphosphate (ATP), and alterations in vascular permeability...
some patients die after a postconcussive syndrome may show evidence of direct parenchymal injury, but in others there is no evidence of damage...
Diffuse Axonal Injury
the surface of the brain is not the only region of damage in traumatic injury, although it is often the most striking ...
the deep centroaxial white matter regions - in the supratentorial compartment, particularly the corpus callosum, paraventricular and hippocampal areas; the brain site, along the cerebral peduncels, brachium conjunctivum, superior coliculi, and deep reticular formation - may also be involved...
the microscopic findings include axonal swellings, indicative of diffuse axonal injury and of focal hemorrhagic lesions...
angular acceleration alone, in the absence of impact, can cause diffuse axonal injury as well as hemorrhage...
as many as 50% of patients who develop coma shortly after trauma, even without cerebral contusions, are believed to have white matter damage and diffuse axonal injury...
the most widely accepted explanation for diffuse axonal injury is that mechanical forces damage the integrity of the axon at the node of Ranvier, with subsequent alterations in axoplasmic flow...
Epidural Hematoma
the epidural space is a potential space - the dura is closely applied to the internal surface of the skull and is fused with the periosteum...
vessels that course within the dura, most importantly the middle meningeal artery, are vulnerable to injury, particularly with skull fractrues...
middle meningeal artery passes through the foramen spinosum...
found in the middle cranial fossa...
trauma to the skull, especially in the region of the temporal bone, can lead to laceration of this artery if the fracture lines cross the course of the vessel...
once a vessel has been torn, the accumulaiton of blood under arterial pressure can caue separation of the dura off the inner surface fo the skull...
the expanding hematoma has a smooth inner contour that compresses the brain surface...clinically, patients can be lucid for several hours between the moment of trauma and the develoment of neurologic signs...
an epidural hematoma may expand rapidly and is a neurosurgical emergency requiring prompt drainage...
Subdural Hematoma
the
bridging vessels
are particularly
prone to tearing along their course through the subdural space; they are the
source of bleeding in most cases of subdural hematoma...
the most commonly accepted mechanism of damage postulates that the brain, floating freely in its bath of CSF, can move within the skull, but the venous sinuses are fixed...
the displacement of the brain that occurs in trauma can tear the veins at the point where they penetrate the dura...
in elderly patients with brain atrophy, the bridging veins are stretched out and the brain has additional space for movement, hence the increased rate of subdural hematomas in these patients, even after relatively minor head trauma...
Falls in older persons, with some degree of cerebral atrophy can result in tearing of the bridging veins, which bare more exposed, and lead to development of a subdural hematoma. Such hematomas can develop over a variable length of time
subdural hematomas most often become clinically manifest wtihin the first 48
hours after injury...
they are most common over the lateral aspects of the cerebral hemispheres and are bilateral in about 10% of cases...
neurologic signs commonly observed are attributable to the pressure exerted on the adjacent brain...there may be focal signs, but often the clinical manifestations are nonlocalizing and include headache or confusion....
in time, there may be slowly progressive neurologic deterioration, but rarely, acute decompensation occurs...
The continued presence of a chronic subdural hematoma leads to headaches, becoming irritable, and acting strangly about a month after the incident, even if it is relatively small.
history of trauma and the interval of several weeks is typical for a chronic subdural. The elderly are at greater risk because cerebral atrophy allows easier tearing of bridging veins.
Global Cerebral Ischemia
ischemic/hypoxic
encephalopathy....
occurs when there is a generalized reduction of cerebral perfusion, such as in cardiac arrest, shock, and severe hypotension...
global hypoxia results in watershed (border zone) infarcts, which typically occur at the border of areas supplied by the anterior and middle cerebral arteries, and laminar necrosis, which is related to the short, penetrating vessels originating from pial arteries...
on macroscopic examination, the brain is swollen, the gyri are widdened, and the sulci are narrowed...the cut surface shows poor demarcation between gray and white matter...
early changes include
the acute neuronal cell change (red neurons) characterized at first by
microvacuolization, then eosinophilia of the neuronal cytoplasm, and later
nuclear pyknosis and karyorrhexis...
subacute changes include necrosis of tissue, influx of macrophages, vascular proliferation, and reactive gliosis...
border zone infarcts "watershed" are wedgeshaped areas of infarction that occur in those regions of the brain and spinal cord that lie at the most distal fields of arterial irrigation...
embolism to the brain occurs from a wide range of origins...cardiac mural thrombi are the most common sources; myocardial infarct, valvular disease, and atrial fibrillation are important predisposing factors...
next in importance are thromboemboli arising in arteries, most often originating over atheromatous plaques within the carotid arteries...
other sources of emboli include paradoxical emboli, particularly in children with cardiac anomalies; emboli associated with cardiac surgery; and emboli of other material (tumor, fat, or air)...
the territory of distribution of the middle cerebral artery is the brain region most frequently affected by embolic infarction; the incidence is about equal in the hemispheres...
Intracerebral (Intraparenchymal) Hemorrhage
spontaneous
(nontraumatic) intraparenchymal hemorrhages occur most commonly in mid to late
adult life, with a peak incidence at about age 60 years...
most are caused by rupture of a small intraparenchymal vessel...
hypertension is the most common underlying cause of primary brain parenchymal hemorrhage, accounting for more than 50% of cases of clinically significant hemorrhage...
may originate in the putamen (50-60% of cases), thalamus, pons, cerebellar hemisphere (rarely), and other regions of the brain...
when the hemorrhges occur in the basal ganglia and thalamus, they are designated ganglionic hemorrhages to distinguish them from those that occur in the ones of the cerebral hemispheres, lobar hemorrhages...
Subarachnoid Hemorrhage and Ruptured Berry Aneurysms
the most frequent cause of clinically significant subarachnoid hemorrhage is rupture of a berry aneurysm...subarachnoid hemorrhage may also result from extension of a traumatic hematoma, rupture of a hypertensive intracerebral hemorrhage into the ventricular system, vascular malformaiton, hematologic disturbances, and tumors...
berry aneurysm is the most common type of intracranial aneurysm...ruptured berry aneurysm is the fourth most common cerebrovascular disorder, after atherosclerotic thrombosis, embolism and hypertensive intraparenchymal hemorrhage...
about 90% of berry aneurysms occur in the anterior circulation and are found near major arterial branch points...
berry aneurysms are the result of congenital defects in the media of blood vessels and are located at the bifurcation of arteries...
the etiologic basis of berry aneurysms is unknown...
there
is an increased risk of their occurrence among patients with heritable systemic
disorders (such as autosomal dominant
polycyctic kidney disease, Ehlers-Danlos syndrome type IV, neurofibromatosis type I, and marfan syndrome) with fibromuscular dysplasia of extracranial arteries and coarctation of the aorta...
cigarette smoking and hypertension (estimated to be present in 54% of patients) are accepted predisposing factors for the development of berry aneurysms...
an unruptured berry aneurysm is a thin-walled outpouching at arterial branch points along the circle of willis or major vessels just beyond...
berry aneurysms
measure a few milimeters to 2 to 3 cm and have a bright red, shiny surface and a
thin translucent wall...
demonstration of the site of rupture requires careful dissection and removal of blood in the unfixed brain...
atheromatous plaques, calcificaiton, or thrombotic occlusion of the sac may be found in the wall or lumen of the aneurysm...
rupture of aneurysm is most frequent complication; 74% of patients with autopsy proven aneurysms have evidence of aneurysmal rupture...
rupture may occur at any time but is often after acute increases in intracranial pressure, such as with straining at stool or sexual orgasm...
blood under arterial pressure is forced into the subarachnoid space, and patients are stricken with sudden, excruciating headache, typically "the worst headace i have ever had"...
and rapidly loose consciousness in minutes...
in acute hemorrhage there is increased risk of vasospastic injury involving vessels other than those originally injured...
this vasospasm can lead to additional ischemic injury...this problem is of greatest significance in cases of basal subarachnoid hemorrhage, in which vasospasm can involve major vessels of the circle of willis...
in the healing phase of subarachnoid hemorrhage, meningeal fibrosis and scarring occur, sometimes leading to obstruction of CSF flow as well as interruption of the normal pathways of CSF resorption...
diagnosis best made with CT scan of head and lumbar puncture...
Arteriovenous Malformation
the lesion consists of a tangle of numerous, abnormally tortuous, misshapen vessels...
males are affected twice as frequently as females, and the lesion is most often recognized clinically between the ages of 10 and 30 years old, presenting as a seizure disorder, an intracerebral hemorrhage, or a subarachnoid hemorrhage...
the most common site is the territory of the anterior cerebral artery, particularly its posterior branches, but they may occur anywhere along the midbain, cerebellum, or sinal cord....
large arteriovenous malformations occurring in the newborn period can lead to CHF b/c of shunt affects, especially if the malformation involves the vein of Galen...
involve vessels in the subarachnoid space extending into brain parenchyma or may occur exclusively within the brain...
in macroscopic appearance, they resemble a tangled network of wormlike vascular channels and have a prominent, pulsatile arteriovenous shunt with high blood flow through the malformation...
on microscopic exminaiton, they are composed of greatly enlarged blood vessels separated by gliotic tissue, often with evidence of prior hemorrhage...
some vessels can be recognized as arteries with duplicatioin and fragmentation of the internal elastic lamina, while others show marked thickening or partial replacement of the media by hyalinized connective tissue...
Lacunar Infarcts
hypertension
affects the deep penetrating arteries and arterioles that supply the
basal ganglia and hemispheric white matter as well as
the brain stem...
the lateral striate arteries are penetrating branches of the middle cerebral artery that supply the caudate, putamen, globus pallidus, and internal capsule...
these cerebral vessels develop arteriolar sclerosis, and some go on to become occluded; the structural changes are similar to those described in vessels outside the CNS...
an important clinical and pathologic outcome of these arterial lesions is the development of single, or multiple, small cavitary infarcts - lacunes, lacunar state...
these are lake like spaces, just a few millimeters wide (not more than 15mm), which occur in the lenticular nucleus, thalamus, internal capsule, deep white matter, caudate nucleus, and pons, in descending order of frequency...
on microscopic examination, they consist of cavities of tissue loss with scattered fat laden macrophages and surrounding gliosis...
depending on their location in the CNS, lacunes can either be clinically silent or cause severe neurologic impairment...affected vessels may also be associated with widening of the perivascular spaces but without tissue infarction...
Transmissible Spongiform Encephalopathies
this group of diseases, include Creutzfeldt Jakob Disease, Gerstmann-Straussler-Scheinker syndrome, fatal familial insomnia, and kuru in humans; scrapie in sheep and goats; mink transmissible encephalopathy; and bovine spongiform encephalopathy (mad cow disease)...
predominatly characterized by spongiform change caused by intracellular vacuoles in neural cells....most develop progressive dementia...
they are all associated with abnormal forms of a specific protein, termed a prion protein (PrP), and are both infectious and transmissible...
these diseases occur when the PrP undergoes a conformational change from its normal alpha-helix isoform to an abnormal beta-pleated sheet isoform, usually termed either PrP scrapie or PrP protease resistant...
accumulation of PrP scrapie in neural tissue appears to be the cause of the pathology in these diseases, but how this material causes the development of cytoplasmic vacuoles and eventual neuronal death is still unknown...
the
progression of dementia in CJD is usually so rapid that there is little, if any,
macroscopic evidence of brain atrophy...
there is a spongiform transformation of the cerebral cortex and, often, deep gray matter structures (caudate, putamen); this consists of a multifocal process that results in the uneven formation of small, apparently empty, microscopic vacuoles of varying sizes within the neuropil and sometimes in the perikaryone of neurons...
in advanced cases, there is severe neuronal loss, reactive gliosis, and sometimes expansion of the vacuolated areas into cystlike spaces ("status spongiosus")...
no inflammatory infiltrate is seen...
vacuoles to be intracytoplasmic and membrane bound in neuronal and glial processes...kuru plaques are extracellular deposits of aggregated abnormal protein; they are congo red-positive as well as PAS-positive...
Creutzfeldt-Jakob Disease
manifests clinically as a rapidly progressive dementia...
worldwide occurance of 1 million per year...
disease has a peak incidence in the seventh decade...
there are well-established cases of iatrogenic transmission, notably by corneal transplantation, deep implantation electrodes, and contaminated preparations of human growth hormone...
the clinical picture is usually typical with the initial subtle changes in memory and behavior followed by a rapidly progressive dementia, often with pronounced involuntary jerking muscle contraction on sudden stimulation (startle myclonus)...
signs of cerebellar dysfunction, usually manifested as ataxia, are present in a minority of patients...
the disease is uniformly fatal, with an average duration of only 7 months, although a few patients have survived for several years...
amyloid deposition...