CNS - neural tube defects, spinal cord lesions, trauma and cerebrovascular disease

Question 1

Neural tube defects - basic principles

Answer 1

Arise from incomplete closure of the neural tube - neural plate invaginates early in gestation to form the neural tube –> runs along the cranial-caudal axis of the embryo - the wall of the nrual tube forms CNS tissue, the hollow lumen forms the ventricles and spinal cord canal, and the neural crest forms the PNSNeural tube defects are associated with low folate levels PRIOR to conceptionDetected during prenatal care by elevated alpha fetoprotein levels in the amniotic fluid and maternal blood

Question 2

Anencephaly

Answer 2

Absence of the skull and brain –> disruption of the cranial end of the neural tube- leads to a frog like appearance of the fetus - results in maternal polyhydramnios since fetal swallowing of amniotic fluid is impaired

Question 3

Spina bifida

Answer 3

Failure of the posterior vertebral arch to close, resulting in a vertebral defect –> disruption of the caudal end of the neural tube - spina bifida occulta –> presents as a dimple or patch of hair overlying the vertebral defect - spina bifida –> presents with cystic protrusion of the underlying tissue through the vertebral defect —> meningocele = protrusion of the meninges—> meningomyelocele = protrusion of meninges and spinal cord

Question 4

Cerebral aqueduct stenosis

Answer 4

Congenital stenosis of the channel that drains CSF from the 3rd to the the 4th ventricle –> leads to accumulation of CSF in the ventricular space = most common cause of hydrocephalus in newborns - CSF is produced by the choroid plexus lining the ventricles- flows from the lateral ventricles into the 3rd ventricle via the interventricular foramen of monro - flows from the 3rd ventricle into the 4th ventricle via the cerebral aqueduct - flows from the 4th ventricle into the subarachnoid space via the foramina of magendie and luschkaPresents with enlarging head circumerence due to dilation of the ventricles - cranial suture lines are not fused early in infancy

Question 5

Dandy walker malformation

Answer 5

Congenital failure of the cerebellar vermis to develop- presents as a massively dilated 4th ventricle (posterior fossa) with an absent cerebellum- often accompanied by hydrocephalus

Question 6

Arnold-chiari malformation (type 2)

Answer 6

Congenital downward displacement of cerebellar vermis and tonsils through the foramen magnum - obstruction of CSF flow commonly results in hydrocephalus - may occur in association with meningomyelocele (most cases) and syringomyelia

Question 7

Syringomyelia

Answer 7

Cystic degeneration of the spinal cord - arises with trauma or in association with arnod-chiari malformationUsuallly occurs at C8-T1 - presents as sensory loss of pain and temperature with sparing of fine touch and position sense in the upper extremities (“cape like” distribution) due to involvement of the anterior white commissure of the spinothalamic tract with sparing of the dorsal columnSyrinx expansion results in involvement of other spinal tracts leading to…- muscle atrophy and weakness with decreased muscle tone and impaired reflexes –> due to damage to lower motor neurons of the anterior horn - horner syndrome with ptosis, miosis and anhidrosis –> due to disruption of the lateral horn of the hypothalamospinal tract

Question 8

Spinothalamic tract

Answer 8

Pain and temperature sensation- first order neuron = peripheral nerves to posterior horn –> cell body is in DRG- second order neuron = arises from posterior horn, immediately crosses over in anterior white commissure, and ascends via the spinothalamic tract to the thalamus - third order neuron = thalamus to cortex

Question 9

Dorsal column-medial lemniscus

Answer 9

Pressure, touch, vibration and proprioception- first order neuron = peripheral nerves to medulla via dorsal column; cell body is in DRG- second order neuron = arises from medulla, crosses over, and ascends via the medial lemniscus to the thalamus- third order = thalamus to cortex

Question 10

Lateral corticospinal tract

Answer 10

Voluntary movement- first order neuron = pyramidal neurons in cortex descend, cross over in medullary pyramids, and synapse on the anterior motor horn of the cord (upper motor neuron)- second order neuron = arises from the anterior motor horn and synapses on muscle (lower motor neuron)

Question 11

Hypothalamospinal tract

Answer 11

Sympathetic input of the face - first order neuron = arises from the hypothalamus and synapses on the lateral horn at T1- second order neuron = arises from lateral horn at T1 and synapses on the superior cervical ganglion (sympathetic)- third order neuron = superior cervical ganglion to eyelids, pupil and skin of face

Question 12

Poliomyelitis

Answer 12

Damage to the anterior motor horn due to poliovirus infectionPresents with lower motor neuron signs- flaccid paralysis with muscle atrophy- fasciculation- weakness with decreased muscle tone- impaired reflexes - negative babinski sign (downgoing toes)

Question 13

Werdig-hoffman disease

Answer 13

Inherited degeneration of the anterior motor horn- autosomal recessive- presents as a floppy baby - death occurs within a few years after birth

Question 14

Amyotrophic lateral sclerosis

Answer 14

Degenerative disorder of upper and lower motor neurons Anterior motor horn degeneration leads to motor neuron signs - flaccid paralysis with muscle atrophy- fasciculation- weakness with decreased muscle tone- impaired reflexes - negative babinski sign (downgoing toes)Lateral corticospinal tract degeneration leads to upper motor neuron signs- spastic paralysis with hyperreflexia (loss of inhibition)- increased muscle tone- positive babinksi sign Atrophy and weakness of hands is an early sign –> lack of sensory impairment distinguishes ALS from syringomyeliaMost cases are sporadic, arising in middle age adults- zinc-copper superoxide dismutase mutation (SOD1) is present in some familial cases –> leads to free radical injury in neurons

Question 15

Friedreich ataxia

Answer 15

Degenerative disorder of the cerebellum and spinal cord- degeneration of the cerebellum leads to ataxia - degeneration of multiple spinal cord tracts leads to loss of vibratory sense and proprioception, muscle weakness in the lower extremities, and loss of deep tendon reflexes Autosomal recessive, due to expansion of an unstable trinucleotide repeat (GAA) in the frataxin gene- frataxin = essential for mitochondrial iron regulation –> loss results in iron buildup with free radical damage Presents in early childhood; patients are wheelchair bound within a few years- associated with hypertrophic cardiomyopathy

Question 16

Epidural hematoma

Answer 16

Collection of blood between the dura and the skull –> classically due to fracture of the temporal bone with rupture of the middle meningeal artery - bleeding separates the dura from the skull- lens shaped lesion on CT- lucid interval may precede neurologic signs - herniation is a lethal complication

Question 17

Subdural hematoma

Answer 17

Collection of blood underneath the dura –> blood covers the surface of the brain - due to tearing of bridging veins that lie between the dura and arachnoid; usually due to trauma- crescent shaped lesion on CT- presents with progressive neurologic signs- increased rate of occurrence in the elderly due to age related cerebral atrophy –> stretches the veins- herniation is a lethal complication

Question 18

Herniation

Answer 18

Displacement of brain tissue to mass effect or increased intracranial pressureTonsillar herniation –> involves displacement of the cerebellar tonsils into the foramen magnus - compression of the brain stem leads to cardiopulmonary arrest Subfalcine herniation –> involves displacement of the cingulate gyrus under the falx cerebri - compression of the anterior cerebral artery leads to infarctionUncal herniation –> involves displacement of the temporal lobe uncus under the tentorium cerebelli- compression of CN III –> eye moves down and out and a dilated pupil- compression of posterior cerebral artery –> infarction of the occipital lobe = contralateral homonymous hemianopsia- rupture of the paramedia artery –> duret (brainstem) hemorrhage

Question 19

Basic principles of cerebrovascular disease

Answer 19

Neurologic deficit due to cerebrovascular compromise –> major cause of morbidity and mortalityDue to ischemia(85%) + hemorrhage (15%)- neurons are dependent on serum glucose as an essential energy source and are particularly susceptible to ischemia –> unergo necrosis within 3-5 minutes

Question 20

Global cerebral ischemia

Answer 20

Global ischemia to the brain –> major etiologies:- low perfusion (e.g. atherosclerosis)- acute decrease in blood flow (e.g. cardiogenic shock)- chronic hypoxia (e.g. anemia)- repeated episodes of hypoglycemia (e.g. insulinoma)Clinical features are based on duration and magnitude of the insult- mild global ischemia –> results in transient confusion with prompt recovery - severe global ischemia –> results in diffuse necrosis; survival leads to “vegetative state”- moderate global ischemia –> leads to infarcts in watershed areas (areas lying between regions fed by the anterior and middle cerebral artery) and damage to highly vulnerable regions such as…—> pyramidal neurons of the cerebral cortex (layers 3,5,6) –> leads to cortical laminar necrosis—> pyramidal neurons of the hippocampus (temporal lobe) –> important in long term memory—> purkinjie layer of the cerebellum –> integrates sensory perception with motor control

Question 21

Ischemic stroke

Answer 21

Regional ischemia to the brain that results in focal neurologic deficits lasting >24 hours –> if symptoms last due to rupture of an atherosclerotic plaque- atherosclerosis usually develops at branch points (e.g. bifurcation of internal carotid and middle cerebral artery in the circle of willis)- results in pale infarct at the periphery of the cortex 2. embolic stroke –> due to thromboemboli- most common source of emboli is the left side of the heart (e.g. in afib)- usually involves the middle cerebral artery- results in a hemorrhagic infarct at the periphery of the cortex 3. lacunar stroke –> occurs secondary to hyaline arteriosclerosis = a complication of hypertension- most commonly involves lenticulostriate vessels, resulting in small cystic areas of infarction- involvement of the internal capsule leads to a pure motor stroke - involvement of the thalamus leads to a pure sensory stroke

Question 22

Morphologic progression of ischemic stroke

Answer 22

Results in liquefactive necrosis- eosinophilic change in the cytoplasm of neurons = red neurons –> early microscopic finding (12 hours after infarction)- 24 hours = necrosis- days 1-3 = infiltration by neutrophils- days 4-7 = microglial cells- weeks 2-3 = gliosis - results in formation of a fluid filled cystic space surrounded by gliosis

Question 23

Intracerebral hemorrhage

Answer 23

Bleeding into brain parenchyma- classically due to rupture of charcot bouchard microaneurysms of the lenticulostriate vessels - complication of hypertension –> treatment of htn reduces incidence by 1/2- basal ganglia is the most common site- presents as severe headache, nausea, vomiting and eventual coma

Question 24

Subarachnoid hemorrhage

Answer 24

Bleeding into the subarachnoid space- presents as a sudden headache (“worst headache of my life”) with nuchal rigidity- lumbar puncture shows xanthochromia = yellow hue due to bilirubin breakdown- most frequently due to rupture of a berry aneurysm - other causes include AV malformations and an anticoagulated state Berry aneurysm = thin walled, saccular outpouchings that lack a media layer, increasing the risk for rupture- most frequently located in the anterior circle of willis at branch points of the anterior communicating artery- associated with Marfan syndrome and autosomal dominant polycystic kidney disease