Introduction

The nervous system is divided into the central nervous system (CNS) and the peripheral nervous system (PNS). The CNS comprises the brain and spinal cord, whereas the PNS consists of all neural structures outside the CNS. The CNS receives, integrates, and responds to sensory information and generates motor output to coordinate behavior and maintain homeostasis (see Image. Major Divisions of the Nervous System).

The brain is an organ of nervous tissue responsible for sensation, movement, emotional responses, communication, cognition, and memory. The skull, meninges, and cerebrospinal fluid (CSF) provide protection. Nervous tissue exhibits extreme fragility, rendering it susceptible to injury from relatively minor forces. Additional protection is conferred by the blood–brain barrier, which restricts the entry of potentially harmful substances circulating in the blood.

The spinal cord, a vital component of the CNS, resides within the vertebral column. Primary functions of the spinal cord include transmitting motor commands from the brain to the peripheral body and relaying sensory information from peripheral receptors to the brain. The vertebrae, meninges, and CSF provide protection.

Structure and Function

Brain

The brain is divided into 2 hemispheres, left and right. Although the hemispheres maintain constant communication, certain functions demonstrate hemispheric lateralization. For example, language functions are typically left-dominant, whereas specific visuospatial and attentional functions are more commonly right-dominant.

Cerebral Cortex

The cerebral cortex forms the outer layer of the cerebrum. Composed of gray matter, this region contains billions of neurons that support high-level functions. The cortex is conventionally divided into 4 lobes separated by major sulci: frontal, parietal, occipital, and temporal.[1]

Frontal lobe

The frontal lobe, located anterior to the central sulcus, is responsible for voluntary motor function, problem-solving, attention, memory, and language. This lobe contains the primary motor cortex and, in the dominant hemisphere, the Broca area. The motor cortex enables precise voluntary movement of skeletal muscles, whereas the Broca area contributes to motor planning for speech production.

Parietal lobe

The parietal lobe, situated posterior to the central sulcus and separated from the occipital lobe by the parietooccipital sulcus, processes somatosensory information and contains the primary somatosensory cortex. Neurons in the parietal lobe receive input from sensory receptors and proprioceptors throughout the body, process this input, and contribute to the perception of touch and body position based on prior experience.

Occipital lobe

The occipital lobe contains the primary visual cortex and serves as the main center for visual processing. This lobe receives visual information from the retina and interprets and recognizes stimuli in the context of prior visual experience.

Temporal lobe

The temporal lobe processes auditory stimuli through the auditory cortex. Sound-induced mechanical vibrations activate mechanoreceptors in cochlear hair cells, and signals are relayed via auditory pathways to the auditory cortex. In the dominant hemisphere, the Wernicke area contributes to language comprehension.

Basal Nuclei

The basal nuclei, also known as the basal ganglia, reside deep within the cerebral hemispheres and include the caudate nucleus, putamen, and globus pallidus. The caudate nucleus and putamen together form the striatum, serving as the primary input region of the basal ganglia. The pallidum, formed by the globus pallidus, functions as the major output region. Through interconnected pathways, the basal ganglia modulate voluntary movement, regulate muscle tone, and contribute to motor coordination.[2]

Thalamus 

The thalamus functions as a major relay center for sensory information. This structure receives afferent input from sensory pathways and processes this information for distribution to appropriate cortical regions. The thalamus also contributes to consciousness and sleep–wake regulation.

Hypothalamus

Although small, the hypothalamus is essential for maintaining homeostasis. This autonomic coordinator links the CNS to the endocrine system via the pituitary gland and regulates functions including heart rate, blood pressure, appetite, thirst, temperature, and circadian rhythms. The hypothalamus synthesizes vasopressin (antidiuretic hormone) and oxytocin and secretes releasing and inhibiting hormones that act on the anterior pituitary, including corticotropin-releasing hormone, gonadotropin-releasing hormone, growth hormone–releasing hormone, thyrotropin-releasing hormone, somatostatin (growth hormone–inhibiting hormone), and dopamine (prolactin-inhibiting hormone).[3]

Pons

The pons is located in the brainstem between the midbrain and medulla oblongata. This structure contains nuclei and tracts that relay signals among the cerebrum, cerebellum, and spinal cord.

Medulla Oblongata

The medulla oblongata, positioned at the inferior aspect of the brainstem, is continuous with the spinal cord at the foramen magnum. This vital brainstem center regulates autonomic functions critical for survival. The medulla modulates respiration via chemoreceptor input related to carbon dioxide and pH. For example, increased carbon dioxide and decreased pH elevate ventilation to enhance elimination of the gas.[4] The medulla also functions as a cardiovascular and vasomotor center, adjusting blood pressure, heart rate, and cardiac contractility according to physiologic demand. Additionally, this structure coordinates protective reflexes, including vomiting, swallowing, coughing, and sneezing.

Cerebellum

The cerebellum coordinates smooth voluntary movement, balance, and motor learning. Subdivisions include the anterior, posterior, and flocculonodular lobes. Communication with adjacent CNS regions occurs via the cerebellar peduncles. The superior cerebellar peduncle connects the cerebellum to the midbrain and primarily transmits efferent output. The inferior cerebellar peduncle links the medulla and cerebellum, carrying critical afferent information, including proprioceptive input involved in balance and posture. The middle cerebellar peduncle conveys predominantly afferent fibers from the pons to the cerebellum. Continuous comparison of intended movement with sensory feedback allows the cerebellum to adjust force, timing, and trajectory to ensure smooth, coordinated contractions.

Limbic System

The limbic system comprises the piriform cortex, hippocampus, septal nuclei, amygdala, nucleus accumbens, hypothalamus, and anterior nuclei of the thalamus.[5] The fornix and associated fiber tracts connect these structures, enabling control over emotion, memory, and motivation. The piriform cortex, part of the olfactory system, resides in the cortical region of the limbic system. Most limbic output is received by the hypothalamus, providing a basis for psychosomatic illnesses in which emotional stressors induce somatic symptoms. For example, a patient experiencing financial stress may present to a primary care physician with hypertension and tachycardia. Subcortical structures, including the septal nuclei, amygdala, and nucleus accumbens, mediate pleasure, emotional processing, and addiction, respectively.

Reticular Formation

The reticular formation is an extensive network of neurons within the brainstem, extending from the superior midbrain to the medulla oblongata. Projecting reticular neurons affect the cerebral cortex, cerebellum, thalamus, hypothalamus, and spinal cord. The reticular formation regulates the body’s level of consciousness through the reticular activating system (RAS). Sensory input from visual, auditory, and somatosensory pathways activates RAS neurons in the brainstem, which relay information to thalamic and cortical targets. Continuous stimulation of these pathways promotes wakefulness and alertness. The RAS also filters repetitive or low-salience stimuli, helping to prevent sensory overload.

Spinal Cord

The spinal cord proper extends from the foramen magnum of the skull to the 1st or 2nd lumbar vertebrae. The cord forms a bidirectional pathway between the brain and the body and divides into 4 regions: cervical, thoracic, lumbar, and sacral. Each region contains multiple segments, totaling 31, with 31 pairs of spinal nerves. The cervical region has 8 nerves, the thoracic region 12, the lumbar region 5, and the sacral region 5. A single coccygeal nerve completes the set of spinal nerves. Each spinal nerve exits the vertebral column through an intervertebral foramen to reach its peripheral distribution.

The width of the spinal cord varies due to the cervical and lumbosacral enlargements. The cervical enlargement occurs at C5 to T1, and the lumbar enlargement at L2 to S3 myelotomes. White matter is located peripherally, whereas gray matter forms the central “butterfly” configuration in axial section, surrounding the CSF-filled central canal. The dorsal, lateral, and ventral horns consist of gray matter.

Neurons in the dorsal horns process sensory information. The ventral horns contain the cell bodies of somatic motor neurons. The lateral horns, prominent in the thoracic and upper lumbar spinal cord, contain autonomic preganglionic neurons. Afferent fibers in the dorsal roots transmit impulses from peripheral sensory receptors to the spinal cord for processing and relay. Efferent fibers exit through ventral roots to innervate skeletal muscle and, via autonomic pathways, regulate smooth muscle, cardiac muscle, and glands.

The spinal cord terminates in a cone-shaped structure called the "conus medullaris," which attaches to the coccyx via the filum terminale. The denticulate ligaments, paired lateral extensions of the pia mater, anchor the spinal cord to the dura mater between spinal nerve roots and further provide stability. These ligaments suspend the cord within the subarachnoid space and limit excessive movement.

Ascending Pathway to the Brain

Sensory information travels from the body to the spinal cord before reaching the brain. Transmission occurs through 1st-, 2nd-, and 3rd-order neurons.

The spinothalamic pathway begins with 1st-order neurons that convey pain and temperature signals from the skin to the spinal cord. Synapses occur immediately with 2nd-order neurons in the dorsal horn. Axons of these 2nd-order neurons cross to the opposite side of the spinal cord and ascend to the thalamus. Thalamic 3rd-order neurons relay these impulses to the somatosensory area of the cerebrum.

Descending Pathway from the Brain

Descending tracts transmit motor signals from the brain to lower motor neurons. Efferent neurons then produce skeletal muscle movement.[6]

Embryology

CNS development begins during the 3rd week of embryogenesis with gastrulation, which forms the trilaminar embryo, and neurulation, which converts dorsal ectoderm into the neural tube that gives rise to the brain and spinal cord.[7] During neurulation, the notochord induces the overlying ectoderm to thicken into the neural plate. The neural plate invaginates to form a neural groove. Neural folds then elevate and fuse in the midline, creating the neural tube.

The cranial and caudal openings of the closing tube are the anterior and posterior neuropores, which temporarily communicate with the amniotic cavity. Closure is time-critical: anterior neuropore closure occurs around day 25, and posterior neuropore closure occurs around day 28 of embryogenesis. Failure of neural tube closure produces major neural tube defects (NTDs), representing incomplete closure along the cranial-caudal axis. Phenotypic expression depends on the specific closure site and the disrupted morphogenetic process.[8]

After neural tube closure, the rostral neural tube expands into primary brain vesicles, early swellings that pattern future brain regions: prosencephalon (forebrain), mesencephalon (midbrain), and rhombencephalon (hindbrain). These primary vesicles subdivide into secondary vesicles that map to adult anatomy. The forebrain gives rise to the telencephalon (cerebral hemispheres) and diencephalon (thalamus, hypothalamus, retina). The mesencephalon (midbrain) persists without subdivision. The hindbrain forms the metencephalon (pons, cerebellum) and myelencephalon (medulla).[9] The lumen of the neural tube persists as the ventricular system and central canal of the spinal cord.

Spinal cord organization follows early dorsoventral patterning into the alar plate, the dorsal sensory interneuron domain, and the basal plate, the ventral motor neuron domain. This pattern establishes functional architecture that later aligns with the adult dorsal and ventral horns. In parallel, neural crest cells, a transient population that detaches from the dorsal neural tube and migrates extensively, form dorsal root ganglia and other PNS structures, providing the anatomic substrate for segmental sensory input.

Cerebral cortical development begins with neural progenitor cells, stem-like cells lining the embryonic ventricles that divide to produce neurons. The number of divisions and the timing of neuronal migration into the cortical plate determine cortical thickness and layering. Most cortical neurons are generated adjacent to the brain’s ventricles within a germinal layer called the "ventricular zone." Dividing cells in this layer, the neural progenitors, act as stem-like precursors that produce neurons.

After neuron generation, cells migrate outward toward the brain surface, often using radial glia, elongated support cells that provide a temporary scaffold for movement. Neurons settle in an inside-out sequence, with earlier neurons remaining in deeper layers and later neurons populating more superficial layers. Disruption of neuron production or migration produces malformations of cortical development and increases the risk of epilepsy.[10][11]

Cortical folding, or gyrification—the formation of gyri and sulci that increases cortical surface area within the skull—follows a reproducible developmental chronology. Human sulcation progresses in 3 broad waves. Primary folds appear from about 20 weeks postmenstrual age (PMA), secondary folds from about 32 weeks PMA, and tertiary folds from about 38 weeks PMA.[12]

The apparent ascent of the spinal cord reflects the differential growth of the vertebral column relative to the neural axis. The conus medullaris, the caudal termination of the spinal cord, reaches a clinically relevant neonatal level by birth. In term infants younger than 3 months evaluated by magnetic resonance imaging, the conus ranged from the superior border of L1 to the top 1/3 of L3, with 96.2% positioned above the superior border of L3. The average conus position lay between the L1-L2 intervertebral disc and the inferior border of L2.[13] This measurement provides an anatomic baseline for interpreting suspected tethered cord and supports lumbar puncture safety planning in neonates when anatomy is uncertain.

Blood Supply and Lymphatics

Blood flow to and from the CNS is closely monitored due to the organ’s importance and delicate structure. The cardiovascular system maintains continuous delivery of oxygenated blood, as even slight reductions in oxygenation can be detrimental. The right common carotid artery arises from the brachiocephalic trunk, whereas the left common carotid artery branches directly from the aorta, which carries oxygen-rich blood from the heart for distribution. Each common carotid artery further divides into the internal and external carotid arteries, supplying the cranium with blood.

Vertebral arteries originate in the neck and branch as they enter the skull through the foramen magnum. These arteries supply the anterior portion of the spinal cord. The vertebral arteries then merge to form the basilar artery, which delivers blood to the brainstem and cerebellum. The circle of Willis provides collateral circulation, ensuring continued blood flow if an artery is compromised. The internal carotid and basilar arteries feed the circle of Willis.[14]

From the internal carotid system, the anterior cerebral artery supplies the medial frontal and parietal cortex, as well as the corpus callosum. The middle cerebral artery perfuses most of the lateral cerebral convexity. Posterior circulation arises from the vertebrobasilar system, which supplies the brainstem and cerebellum and contributes to perfusion of the occipital and inferomedial temporal lobes.

Venous drainage occurs through superficial cortical veins and the deep venous system into the dural venous sinuses, and ultimately into the internal jugular veins. The main dural venous sinuses include the superior sagittal, straight, transverse, and sigmoid.

Spinal cord perfusion follows a segmental pattern. Cervical, thoracic, and lumbar segmental arteries provide radiculomedullary branches to the cord, although only a few remain large and functionally significant in adults. In the thoracolumbar region, the largest radiculomedullary feeder is the artery of Adamkiewicz.

Meningeal lymphatic vessels reside within the dura, with concentrations along the dural venous sinuses and major meningeal vessels. These vessels collect CSF-derived fluid, macromolecules, and trafficking immune cells from meningeal and perivascular compartments. Collected material drains toward extracranial lymphatics and deep cervical lymph nodes via skull base outlets.[15]

Nerves

Cranial nerve nuclei consist of collections of gray matter within the brainstem that give rise to, or receive input from, cranial nerve fibers. Nuclei are arranged in longitudinal columns organized around the sulcus limitans, a shallow groove in the brainstem that marks the embryologic boundary between the basal and alar plates. Structures medial to the sulcus limitans perform motor functions, whereas structures lateral to the groove perform sensory functions.

Somatic motor nuclei, innervating skeletal muscle derived from somites, lie closest to the midline and include the oculomotor, trochlear, abducens, and hypoglossal nuclei. Branchial motor nuclei, located more laterally, supply muscles derived from the pharyngeal arches. Parasympathetic nuclei and sensory nuclei, including the trigeminal sensory nuclear complex and the solitary nucleus, occupy progressively more lateral positions.

Within the spinal cord, nerve fibers interface with the CNS at defined root entry and exit zones. Dorsal rootlets carrying sensory afferents enter the cord at the posterolateral sulcus, a longitudinal groove that defines the dorsal root entry zone and transitions peripheral fibers into central nervous tissue. Sensory fibers project into the dorsal horn. Ventral rootlets exit the cord at the anterolateral sulcus, arising from motor neurons in the anterior horn, as well as preganglionic sympathetic neurons in the intermediolateral cell column between T1 and L2. Dorsal and ventral roots traverse the subarachnoid space, pass through dural sleeves, and unite within the intervertebral foramen to form mixed spinal nerves.

Physiologic Variants

Cortical gray matter volume reaches a maximum at age 5.9 years, followed by a gradual reduction throughout adulthood. White matter volume peaks at 28.7 years, with subsequent decline accelerating after 50 years. Subcortical gray matter attains its highest volume at 14.4 years. CSF volume increases until 2 years of age, remains stable until 30 years, and then rises again, with the rate of increase accelerating in the 6th decade.[16]

In routine practice, the mean CSF opening pressure measures 17.5 cm H2O (range: 4.0–30.0 cm H2O). Higher pressures are associated with the male sex, younger age, and elevated body mass index (BMI). Pragmatic upper-limit thresholds have been proposed as 30 cm H2O in male individuals (or 25 cm H2O if age exceeds 70 years) and 25 cm H2O in female individuals (or 27.5 cm H2O if BMI exceeds 30).[17]

Physiologic variants exist within the cerebral vascular system. In a community sample using time-of-flight magnetic resonance angiography, a complete circle of Willis occurred in 11.9% of participants. The most common variant, observed in 27.8%, lacked both posterior communicating arteries. The prevalence of missing segments increases with age.[18] Transverse sinus asymmetry is common on magnetic resonance venography, with left transverse sinus hypoplasia present in 21.3% of individuals.[19]

Surgical Considerations

Anesthesia is a controlled state of temporary loss of sensation that enables the performance of painful medical procedures that would otherwise be unfeasible. Types of anesthesia include general, sedation, and local. All forms disrupt cellular and intracellular communication within the CNS and PNS.

General anesthesia typically involves an analgesic, a paralytic (neuromuscular blocker, NMB), and an amnestic. These agents act together to render the patient unconscious and immobile. CNS activity undergoes suppression during general anesthesia, producing a total loss of sensation. NMBs require intubation and mechanical ventilation.

Depolarizing NMBs, such as succinylcholine, bind to postsynaptic cholinergic receptors, causing initial depolarization. The prolonged presence of these NMBs on the receptor prevents repolarization and subsequent depolarizations. Nondepolarizing NMBs, such as vecuronium, act as competitive antagonists. These drugs block postsynaptic cholinergic receptors without producing agonist activity, preventing acetylcholine from binding and triggering muscle contraction.[20]

During regional anesthesia, only the target portion of the body is numbed. Neuraxial techniques, including spinal and epidural anesthesia, deliver local anesthetic near the spinal cord. Spinal anesthesia involves the direct injection of medication into the subarachnoid space to mix with CSF. Epidural anesthesia entails injection into the epidural space outside the dural sac.

Anesthetic procedures carry inherent risks. Conditions that increase the likelihood of complications include obesity, diabetes, hypertension, and diseases affecting the respiratory or cardiovascular systems.[21]

Neurosurgeons undergo specialized training to diagnose and treat injuries or diseases affecting the CNS. Operative management targets neurological disorders, such as tumors, stroke, head and spinal injuries, and chronic pain. Surgical procedures carry risks, particularly when operating on delicate nervous tissue within the brain and spinal cord. Complications of brain surgery may include intracranial hemorrhage, deficits in speech, memory, or coordination, stroke, cerebral edema, paralysis, or potential coma.

The brain and spinal cord reside within rigid osseous compartments. This principle is described by the Monro-Kellie Doctrine. Since the skull volume is fixed, any increase in intracranial contents, including blood, edema, or hydrocephalus, must be offset by a decrease in another component, such as CSF or venous blood. Once compensatory mechanisms are exhausted, even small volume increases produce rapid spikes in intracranial pressure, compromising perfusion and compressing neural tissue. These conditions typically require urgent intervention to restore perfusion and relieve pressure.

Operative planning for surgical brain lesions begins with precise anatomic localization based on neurologic examination and neuroimaging. Localization defines the lesion’s spatial relationship to eloquent cortex, subcortical white matter tracts, cranial nerves, and critical vascular territories. This anatomic mapping guides the selection of the surgical corridor, informs the likelihood of achieving gross total resection, and allows estimation of procedure-specific neurologic risk. Accurate preoperative localization remains central to balancing oncologic or decompressive goals against the risk of permanent functional deficit.

Clinical Significance

The clinical significance of the CNS encompasses a broad spectrum of pathologies, including vascular insults, traumatic injuries, neurodegenerative disorders, and demyelinating conditions. Precise localization of function within the CNS allows specific patient symptoms to serve as direct indicators of the underlying anatomical lesion. Disruption of blood supply, structural integrity, or neurochemical signaling produces characteristic deficits, enabling clinicians to localize damage to cortical areas, white matter tracts, or spinal segments. The following section highlights key clinical conditions that illustrate the relationship between CNS anatomy and pathologic dysfunction.

Wernicke Aphasia

Wernicke aphasia occurs most commonly following a hemorrhagic or ischemic stroke. Infarction or hemorrhage in the left middle cerebral artery prevents oxygenated blood from reaching the Wernicke area, located in the superior temporal gyrus. Patients with Wernicke aphasia produce fluent speech that is articulate but semantically meaningless (“word salad”) and demonstrate significant impairment in language comprehension.

Broca Aphasia

Broca aphasia, also referred to as "expressive aphasia," arises from stroke, brain tumor, or traumatic brain injury (TBI). Stroke in the Broca area, situated in the inferior frontal gyrus, causes oxygen deprivation and irreversible neuronal damage. Individuals with Broca aphasia retain comprehension and know the content of their intended speech but cannot articulate words to communicate effectively.[22]

Traumatic Brain Injuries

TBIs occur when normal brain activity is disrupted, often resulting from sports injuries, motor vehicle collisions, or penetrating trauma. Clinical manifestations vary according to injury severity. Mild TBI, such as a concussion, may produce temporary dizziness or a brief loss of consciousness. Contusions involving the brainstem can result in coma.

Severe TBI may cause epidural, subdural, intraparenchymal, or subarachnoid hemorrhage, as well as cerebral edema. Accumulation of blood from a hematoma elevates intracranial pressure and displaces brain tissue across rigid intracranial structures, a process termed "herniation." In uncal herniation, the uncus of the temporal lobe shifts medially past the tentorium cerebelli, compressing the adjacent brainstem and the 3rd cranial nerve. Clinically, this pathophysiologic process often presents as a fixed, dilated pupil.

Tonsillar herniation occurs when the cerebellar tonsils are forced downward through the foramen magnum. Downward displacement compresses the medulla oblongata, rapidly compromising autonomic centers that regulate respiration.

Cerebrovascular Accidents

Cerebrovascular accidents (CVAs), or strokes, occur when the brain is deprived of oxygenated blood, leading to hypoxia and tissue death. The most common cause is a blood clot (embolus) traveling to a cerebral artery. Clinical manifestations vary according to the vessel affected. For example, occlusion of the middle cerebral artery may produce contralateral paralysis and slurred speech. Transient ischemic attacks are brief episodes of stroke-like symptoms that resolve spontaneously. Rapid intervention is essential to minimize ischemic injury. Management strategies include administration of tissue plasminogen activator for thrombolysis or performance of mechanical thrombectomy.

Alzheimer Disease

Alzheimer disease constitutes a prevalent form of dementia characterized by progressive degeneration of brain cells and neural connections. The disease manifests as gradual memory loss and cognitive decline.[23] Neuropathologic features include extracellular β-amyloid plaques and intraneuronal τ neurofibrillary tangles. These abnormal protein aggregates contribute to progressive neuronal dysfunction and cell loss, with the hippocampus, medial temporal lobe, and basal forebrain commonly affected.

Parkinson Disease

Parkinson disease is a neurodegenerative disorder characterized by deterioration of dopamine-releasing neurons in the substantia nigra.[24] Dopamine deficiency produces tremors, impaired coordination, and postural instability. Symptoms often begin as a “pill-rolling” tremor in one hand and progress to bradykinesia, muscular rigidity, and a mask-like facial expression. Although no cure exists, symptom management is possible. Levodopa crosses the blood-brain barrier and undergoes conversion to dopamine for CNS utilization. Deep brain stimulation offers a surgical option to control tremors but does not halt disease progression.

Huntington Disease

Huntington disease is an autosomal dominant, progressive neurodegenerative disorder caused by the expansion of a cytosine-adenine-guanine (CAG) repeat in the HTT gene. Normal alleles typically contain 35 or fewer repeats, whereas affected individuals generally have 36 or more repeats, with 40 or more repeats often associated with full penetrance. Larger expansions correlate with earlier disease onset. Mutant huntingtin protein induces neuronal dysfunction and loss, primarily in the striatum (caudate and putamen), with progressive cortical involvement. Clinical features include motor abnormalities, frequently chorea, psychiatric disturbances, and cognitive decline, ultimately resulting in severe disability. Disease course varies, but median survival is approximately 15 to 20 years after symptom onset.

Spinal Cord Traumas

Clinical manifestations of spinal cord injuries depend on the anatomic level and extent of the lesion. Sensory deficits occur when the dorsal columns or spinothalamic tracts sustain damage. Motor outcomes vary according to the specific neural elements affected. Injury to the ventral roots or ventral horns, representing lower motor neurons, prevents nerve impulses from reaching muscles and produces flaccid paralysis. In contrast, damage to descending motor tracts, representing upper motor neurons, results in spastic paralysis due to loss of central inhibition and subsequent involuntary muscle contraction. The level of injury determines limb involvement. Cervical lesions typically result in quadriplegia, whereas lesions between T1 and L1 cause paraplegia.

Poliomyelitis

Poliomyelitis is a viral infection of the spinal cord caused by poliovirus and transmitted via the fecal–oral route. The virus selectively destroys lower motor neurons in the anterior (ventral) horn, producing acute flaccid paralysis with preserved sensation. The disease is effectively preventable through vaccination.[25]

Amyotrophic Lateral Sclerosis

Amyotrophic lateral sclerosis, also known as Lou Gehrig disease, is a progressive neurodegenerative disorder characterized by degeneration of both upper and lower motor neurons, resulting in loss of voluntary motor function. Etiology is heterogeneous and incompletely understood. Proposed mechanisms include glutamate-mediated excitotoxicity, mitochondrial dysfunction, protein aggregation, and impaired axonal transport. Clinically, Amyotrophic lateral sclerosis manifests as progressive muscle weakness, atrophy, and fasciculations, followed by involvement of bulbar and respiratory musculature, producing dysarthria, dysphagia, and respiratory failure. Riluzole, a glutamate-modulating agent, modestly slows disease progression and prolongs survival.

Multiple Sclerosis

Multiple sclerosis is a chronic immune-mediated demyelinating disease of the CNS characterized by inflammatory destruction of myelin and oligodendrocytes, resulting in impaired neural conduction. Multiple sclerosis most commonly affects young adults, with a higher prevalence in women. Clinical manifestations are heterogeneous and may include optic neuritis with visual loss, sensory disturbances or pain, motor weakness, ataxia, or impaired coordination, often following a relapsing or progressive course. Disease severity and progression vary widely among individuals. Disease-modifying therapies target immune dysregulation to reduce relapse frequency, delay disability progression, and limit inflammatory CNS injury.

Review Questions

• Access free multiple choice questions on this topic.
• Comment on this article.

References

1.

Shipp S. Structure and function of the cerebral cortex. Curr Biol. 2007 Jun 19;17(12):R443-9. [PubMed: 17580069]

2.

Lanciego JL, Luquin N, Obeso JA. Functional neuroanatomy of the basal ganglia. Cold Spring Harb Perspect Med. 2012 Dec 01;2(12):a009621. [PMC free article: PMC3543080] [PubMed: 23071379]

3.

Flament-Durand J. The hypothalamus: anatomy and functions. Acta Psychiatr Belg. 1980 Jul-Aug;80(4):364-75. [PubMed: 7025580]

4.

Nattie E, Li A. Central chemoreceptors: locations and functions. Compr Physiol. 2012 Jan;2(1):221-54. [PMC free article: PMC4802370] [PubMed: 23728974]

5.

Rajmohan V, Mohandas E. The limbic system. Indian J Psychiatry. 2007 Apr;49(2):132-9. [PMC free article: PMC2917081] [PubMed: 20711399]

6.

Canedo A. Primary motor cortex influences on the descending and ascending systems. Prog Neurobiol. 1997 Feb;51(3):287-335. [PubMed: 9089791]

7.

Kuwar Chhetri P, Das JM. StatPearls [Internet]. StatPearls Publishing; Treasure Island (FL): Jul 24, 2023. Neuroanatomy, Neural Tube Development and Stages. [PMC free article: PMC557414] [PubMed: 32491346]

8.

Engelhardt DM, Martyr CA, Niswander L. Pathogenesis of neural tube defects: The regulation and disruption of cellular processes underlying neural tube closure. WIREs Mech Dis. 2022 Sep;14(5):e1559. [PMC free article: PMC9605354] [PubMed: 35504597]

9.

Stiles J, Jernigan TL. The basics of brain development. Neuropsychol Rev. 2010 Dec;20(4):327-48. [PMC free article: PMC2989000] [PubMed: 21042938]

10.

Prodromidou K, Matsas R. Evolving features of human cortical development and the emerging roles of non-coding RNAs in neural progenitor cell diversity and function. Cell Mol Life Sci. 2021 Dec 18;79(1):56. [PMC free article: PMC11071749] [PubMed: 34921638]

11.

Russ JB, Agarwal S, Venkatesan C, Scelsa B, Vollmer B, Tarui T, Pardo AC, Lemmon ME, Mulkey SB, Hart AR, Nagaraj UD, Kuller JA, Whitehead MT, Cohen JL, Gebb JS, Glenn OA, Norton ME, Gano D. Fetal malformations of cortical development: review and clinical guidance. Brain. 2025 Jun 03;148(6):1888-1903. [PMC free article: PMC12129737] [PubMed: 40048696]

12.

de Vareilles H, Rivière D, Mangin JF, Dubois J. Development of cortical folds in the human brain: An attempt to review biological hypotheses, early neuroimaging investigations and functional correlates. Dev Cogn Neurosci. 2023 Jun;61:101249. [PMC free article: PMC10311195] [PubMed: 37141790]

13.

Sun M, Tao B, Gao G, Wang H, Shang A. Determination of the normal conus medullaris level in term infants: the role of MRI in early infancy. J Neurosurg Pediatr. 2022 Jan 01;29(1):100-105. [PubMed: 34653991]

14.

Vrselja Z, Brkic H, Mrdenovic S, Radic R, Curic G. Function of circle of Willis. J Cereb Blood Flow Metab. 2014 Apr;34(4):578-84. [PMC free article: PMC3982101] [PubMed: 24473483]

15.

das Neves SP, Delivanoglou N, Da Mesquita S. CNS-Draining Meningeal Lymphatic Vasculature: Roles, Conundrums and Future Challenges. Front Pharmacol. 2021;12:655052. [PMC free article: PMC8113819] [PubMed: 33995074]

16.

Bethlehem RAI, Seidlitz J, White SR, Vogel JW, Anderson KM, Adamson C, Adler S, Alexopoulos GS, Anagnostou E, Areces-Gonzalez A, Astle DE, Auyeung B, Ayub M, Bae J, Ball G, Baron-Cohen S, Beare R, Bedford SA, Benegal V, Beyer F, Blangero J, Blesa Cábez M, Boardman JP, Borzage M, Bosch-Bayard JF, Bourke N, Calhoun VD, Chakravarty MM, Chen C, Chertavian C, Chetelat G, Chong YS, Cole JH, Corvin A, Costantino M, Courchesne E, Crivello F, Cropley VL, Crosbie J, Crossley N, Delarue M, Delorme R, Desrivieres S, Devenyi GA, Di Biase MA, Dolan R, Donald KA, Donohoe G, Dunlop K, Edwards AD, Elison JT, Ellis CT, Elman JA, Eyler L, Fair DA, Feczko E, Fletcher PC, Fonagy P, Franz CE, Galan-Garcia L, Gholipour A, Giedd J, Gilmore JH, Glahn DC, Goodyer IM, Grant PE, Groenewold NA, Gunning FM, Gur RE, Gur RC, Hammill CF, Hansson O, Hedden T, Heinz A, Henson RN, Heuer K, Hoare J, Holla B, Holmes AJ, Holt R, Huang H, Im K, Ipser J, Jack CR, Jackowski AP, Jia T, Johnson KA, Jones PB, Jones DT, Kahn RS, Karlsson H, Karlsson L, Kawashima R, Kelley EA, Kern S, Kim KW, Kitzbichler MG, Kremen WS, Lalonde F, Landeau B, Lee S, Lerch J, Lewis JD, Li J, Liao W, Liston C, Lombardo MV, Lv J, Lynch C, Mallard TT, Marcelis M, Markello RD, Mathias SR, Mazoyer B, McGuire P, Meaney MJ, Mechelli A, Medic N, Misic B, Morgan SE, Mothersill D, Nigg J, Ong MQW, Ortinau C, Ossenkoppele R, Ouyang M, Palaniyappan L, Paly L, Pan PM, Pantelis C, Park MM, Paus T, Pausova Z, Paz-Linares D, Pichet Binette A, Pierce K, Qian X, Qiu J, Qiu A, Raznahan A, Rittman T, Rodrigue A, Rollins CK, Romero-Garcia R, Ronan L, Rosenberg MD, Rowitch DH, Salum GA, Satterthwaite TD, Schaare HL, Schachar RJ, Schultz AP, Schumann G, Schöll M, Sharp D, Shinohara RT, Skoog I, Smyser CD, Sperling RA, Stein DJ, Stolicyn A, Suckling J, Sullivan G, Taki Y, Thyreau B, Toro R, Traut N, Tsvetanov KA, Turk-Browne NB, Tuulari JJ, Tzourio C, Vachon-Presseau É, Valdes-Sosa MJ, Valdes-Sosa PA, Valk SL, van Amelsvoort T, Vandekar SN, Vasung L, Victoria LW, Villeneuve S, Villringer A, Vértes PE, Wagstyl K, Wang YS, Warfield SK, Warrier V, Westman E, Westwater ML, Whalley HC, Witte AV, Yang N, Yeo B, Yun H, Zalesky A, Zar HJ, Zettergren A, Zhou JH, Ziauddeen H, Zugman A, Zuo XN, 3R-BRAIN. AIBL. Alzheimer’s Disease Neuroimaging Initiative. Alzheimer’s Disease Repository Without Borders Investigators. CALM Team. Cam-CAN. CCNP. COBRE. cVEDA. ENIGMA Developmental Brain Age Working Group. Developing Human Connectome Project. FinnBrain. Harvard Aging Brain Study. IMAGEN. KNE96. Mayo Clinic Study of Aging. NSPN. POND. PREVENT-AD Research Group. VETSA. Bullmore ET, Alexander-Bloch AF. Brain charts for the human lifespan. Nature. 2022 Apr;604(7906):525-533. [PubMed: 35388223]

17.

Bø SH, Lundqvist C. Cerebrospinal fluid opening pressure in clinical practice - a prospective study. J Neurol. 2020 Dec;267(12):3696-3701. [PMC free article: PMC7674322] [PubMed: 32681283]

18.

Hindenes LB, Håberg AK, Johnsen LH, Mathiesen EB, Robben D, Vangberg TR. Variations in the Circle of Willis in a large population sample using 3D TOF angiography: The Tromsø Study. PLoS One. 2020;15(11):e0241373. [PMC free article: PMC7608873] [PubMed: 33141840]

19.

Goyal G, Singh R, Bansal N, Paliwal VK. Anatomical Variations of Cerebral MR Venography: Is Gender Matter? Neurointervention. 2016 Sep;11(2):92-8. [PMC free article: PMC5018554] [PubMed: 27621945]

20.

Raghavendra T. Neuromuscular blocking drugs: discovery and development. J R Soc Med. 2002 Jul;95(7):363-7. [PMC free article: PMC1279945] [PubMed: 12091515]

21.

Gottschalk A, Van Aken H, Zenz M, Standl T. Is anesthesia dangerous? Dtsch Arztebl Int. 2011 Jul;108(27):469-74. [PMC free article: PMC3147285] [PubMed: 21814522]

22.

Fridriksson J, Fillmore P, Guo D, Rorden C. Chronic Broca's Aphasia Is Caused by Damage to Broca's and Wernicke's Areas. Cereb Cortex. 2015 Dec;25(12):4689-96. [PMC free article: PMC4669036] [PubMed: 25016386]

23.

Schachter AS, Davis KL. Alzheimer's disease. Dialogues Clin Neurosci. 2000 Jun;2(2):91-100. [PMC free article: PMC3181599] [PubMed: 22034442]

24.

DeMaagd G, Philip A. Parkinson's Disease and Its Management: Part 1: Disease Entity, Risk Factors, Pathophysiology, Clinical Presentation, and Diagnosis. P T. 2015 Aug;40(8):504-32. [PMC free article: PMC4517533] [PubMed: 26236139]

25.

Mehndiratta MM, Mehndiratta P, Pande R. Poliomyelitis: historical facts, epidemiology, and current challenges in eradication. Neurohospitalist. 2014 Oct;4(4):223-9. [PMC free article: PMC4212416] [PubMed: 25360208]

Disclosure: Konstantinos Margetis declares no relevant financial relationships with ineligible companies.

Disclosure: Vamsi Reddy declares no relevant financial relationships with ineligible companies.

Disclosure: Paramvir Singh declares no relevant financial relationships with ineligible companies.