Chapter 28: Paraneoplastic & Developmental Disorders of the Nervous System Flashcards
Paraneoplastic Neurological Disorders (PNDs)
- Occur when an antitumor immune response is directed against an “onconeural antigen” (antigen that is alsopresent on both tumor & nervous cells).
- PND may be first symptom of neoplastic process.
- May be diffuse or localized.
- Major onconeural antigens are either intracellular antigens (with funny names like Hu, Yo, Ri, & Ma) or extracellular proteins (like NT receptors/ion channels).
Anencephaly
- Absence of the brain/spinal cord. Leads to “frog-like” appearance of fetus (real sensitive, Sattar).
- Somewhat genetic/hereditary.
- Results from failure of cephalad (rostral) closure of neural tube (aka anterior neuropore).
- In place of cerebrum is “cerebrovasculosa” = highly vascularized/disorganized neuroglial tissue.
Folic acid
Required for proper neural tube closure. Supplementations has led to significant decrease in Neural Tube Defects (NTDs), especially anencephaly & spina bifida.
Some drugs, notable retinoids for acne & valproic acid for seizure, must be avoided during pregnancy for risk of NTD.
Spina Bifida
A set of NTDs that arise from failure of caudal neural tube closure. Usually in the lumbar region. 4 subtypes: 1) spina bifida occulta, 2) meningocele, 3) meningomyelocele, 4) rachischisis.
Spina bifida occulta
small defect of posterior vertebral arch. usually asymptomatic, presenting only with small patch of hair or dimple on lower back overlying defect
Meningocele
Defect of vertebra and soft tissue that allows protrusion of the meninges as a visible, fluid-filled sac. Apex may ulcerate, allowing contamination of CSF. Spinal cord itself remains in its normal location.
Meningomyelocele
Defect of vertebra and soft tissue that allows protrusion of the meninges as a visible, fluid-filled sac. Apex may ulcerate, allowing contamination of CSF. Spinal cord & nerve roots become entrapped in the external sac, with severe neurological consequences (e.g. lower extremity sensorimotor & excretory defects). Spinal cord becomes flattened & ribbon-like.
Rachischisis
Extreme NTD in which the spinal column is a gaping canal without a recognizable spinal cord. Usually fatal in utero.
Syringomyelia
A congenital tubular cavitation (syrinx) that extends for variable distances throughout the spinal cord. Progress during life and usually not clinically manifested until adulthood. Cause bilateral pain sensation deficits only at the spinal level of the defect (due to crossing fibers!).
Arnold-Chiari Malformation
Compaction of the brainstem and cerebellum into a shallow, bowl-shaped posterior fossa. Often associated with syringomyelia or meningomyelocele (which can anchor spinal cord and yank it down during development). NTD & segmentation defect. exhibits:
- herniation of cerebral vermis through foramen magnum
- caudal displacement/kinking of the dorsal brainstem
- Cerebral aqueduct stenosis, leading to hydrochephalus
- Polymicrogyria (don’t worry theres a card on this too)
- Beak-shaped dorsal protrusion of inferior colliculi/quadrigeminal plate
Holoprosencephaly
Interhemispheric fissure is completely or partially absent, resulting in one common ventricle. Alobar, lobar and arrhinencephaly are the three subtypes, in decreasing severity. With the first two, if the patient survives past a few weeks or months, it is usually with severe mental retardation and seizures.
Congenital Atresia of the Aqueduct of Sylvius
Most common cause of congenital obstructive hydrocephalus; results from deranged midrbain development. May show multiple atretic channels, or an aqueduct narrowed by gliosis.
(Aqueduct of Sylvius = cerebral aqueduct)
Schizencephaly
Cortical malformations arise from developmental defects of neuroglial proliferation in, and migration from, the germinal matrix. If the defect is focal, only the overlying cortex if affected, and this is called schizencephaly. If the defect is diffuse, it is usually genetically based, and called lissencephaly.
Examples: Heterotopias, polymicrogyria, pachygyria.
Lissencephaly
Most severe congenital disorder of cortical development. Most have LIS1 defect, causing failure of neurons to migrate from germinal matrix. Surface of cerebral cortex is smooth or has imperfectly formed gyri. More likely to be genetically caused than schizencephaly, and more global and severe.
Heterotopias
“Focal disturbances in neural migration that lead to nodules of ectopic neurons and glia, usually in white matter. They are often associated with mental retardation and seizures and may be caused by maternal alcoholism” -Rubin
