GENERAL ORGANIZATION OF NERVOUS SYSTEM
Nervous system is broadly divided into central nervous system (CNS), peripheral nervous system (PNS), and autonomic nervous system (Fig. 1). CNS includes brain and spinal cord; whereas, PNS includes all neural structures outside CNS including 12 pairs of cranial nerves (CNs), 31 pairs of spinal nerves, and their ganglia. Autonomic nervous system consists of sympathetic and parasympathetic nervous systems.
There are two types of cells in nervous system—neurons and neuroglial cells.
Neurons
Neurons are the excitable cells, which have a cell body, dendrites, and axon (Fig. 2). Dendrites receive the signal from another neuron and send it to the cell body. Axon passes the signal from the cell body to other neurons.
- Cell body: A collection of cell bodies in CNS is called a nucleus (e.g., cranial nerve nucleus in brainstem). Ganglion is the collection of nerve cell bodies in PNS (e.g., dorsal root ganglia and trigeminal ganglia).
- Axons: Axon of a neuron is called nerve fiber. A bundle of nerve fibers in CNS is called a tract (e.g., corticospinal tract and corticobulbar tract). Whereas, a collection of nerve fibers in PNS is called a nerve (e.g., median nerve and radial nerve).
Neurons are the functional unit of nervous system and cannot regenerate (except in parts of hippocampus and olfactory bulb). When neurons fire, an action potential is generated, which traverses the axon to reach dendrite of the next neuron through a junction called synapse. A synapse consists of a presynaptic terminal and a postsynaptic terminal. The chemical neurotransmitters like acetylcholine and adrenaline carry the impulse across the two terminals. The neurotransmitters may be excitatory (noradrenaline, adrenaline, glutamate, and aspartate) or inhibitory (glycine and GABA).
Depending on the function of neurons, they are classified as—motor neurons (neurons that stimulate skeletal and smooth muscle), sensory neurons (neurons that transmit sensation to CNS), and interneurons (connecting neurons). Motor neurons that transmit signals from the brain to the anterior horn cell or from the brain till the CN nuclei are called upper motor neurons (UMNs). Motor neurons located in spinal cord that transmit signals from the spinal cord to muscle or those that transmit from CN nuclei to muscles of head and neck are called lower motor neurons (LMNs) (Fig. 3). A lesion in the motor neuron is accordingly categorized as an UMN lesion or a LMN lesion.
Upper motor neurons have their cell bodies in the motor area of the cerebral cortex. Their axons descend through the internal capsule and brainstem to end at spinal cord (corticospinal tract) or end at CN nuclei in the brainstem (corticobulbar tract). A lesion of corticospinal tract or corticobulbar tract is called as UMN lesion. LMNs have their cell bodies at the spinal cord (called anterior horn cell) or at the brainstem (in case of CN nuclei). The anterior horn cells of the spinal cord supply the skeletal muscles of the limbs and trunk. CN nuclei at the brainstem supply skeletal and smooth muscles of head and neck. A lesion anywhere along this pathway is called LMN lesion.5
Clinical relevance: UMN lesion could result from a lesion in corticospinal tract (resulting in pyramidal signs like spasticity, motor weakness, and brisk deep tendon reflexes) or corticobulbar tract (resulting in pseudobulbar palsy). Corticospinal or corticobulbar tract can be affected anywhere in its pathway from cerebral cortex, internal capsule, or brainstem. Similarly, CN palsy such as facial nerve palsy can result from an UMN lesion (if the lesion is above the CN nucleus, similar to the lesion of corticobulbar fibers) or a LMN lesion (lesion anywhere along the nerve, e.g., along the facial nerve course as in Bell's palsy). LMN lesion could result from a lesion anywhere in the pathway of LMN—anterior horn cell (e.g., poliomyelitis), nerve (e.g., Guillain–Barré syndrome), neuromuscular junction (e.g., myasthenia), or muscle (e.g., viral myositis).
Neuroglial Cells
Glia means “glue” in Latin. It was believed that neuroglial cells only provide physical support to neurons, but their functions are far wider. Neuroglial cells include astrocytes, oligodendrocytes, microglia, and ependymal cells. Nerve cells (cell body) embedded in neuroglia comprise gray matter; whereas, nerve fibers or axons embedded in neuroglial cells comprise white matter.
- Astrocytes form a supporting framework for nerve cells and nerve fibers.
- Oligodendrocytes are responsible for formation of myelin sheath of nerve fibers of CNS. Schwann cells form the myelin sheath of peripheral nerves.
- Microglial cells are specialized reticuloendothelial cells in CNS.
- Ependymal cells line the cavities of the brain and assist in circulation of cerebrospinal fluid.
Clinical relevance: Mild injuries result in neurons to undergo swelling, with displacement of nucleus and Nissl granules. Neurons tend to recover from this state. In severe injury, there is degeneration followed by phagocytosis by microglial cells. Microglia migrates to and proliferates at the site of injury in inflammatory and degenerative diseases of CNS. There is fibrous proliferation of neuroglial cells resulting in gliosis. This proliferation does not compensate for neuronal loss, rather, leads to volume loss. In contrast, on surgical excision, there is no residual traumatized nervous tissue and thus there is minimal or no gliosis.
PERIPHERAL NERVOUS SYSTEM
Peripheral nerves are bundles of nerve fibers enveloped by Schwann cells, which form its myelin sheath. A nerve fiber can be myelinated or non-myelinated. Myelin sheath is segmented at regular interval called nodes of Ranvier (Fig. 2). It enhances the conduction of impulses across the nerve.
There are three types of peripheral nerve fibers—type-A fibers (myelinated large diameter fibers), type-B fibers (medium diameter and myelinated fibers), and type-C fibers (small diameter and nonmyelinated fibers). Majority of PNS (motor and sensory) has type-A fibers, which have the highest conduction velocity. Type-A fibers serve to carry proprioception (Aα), touch/pressure (Aβ), motor signals to muscle spindle (Aγ), and pain/cold/touch sensation (Aδ). Type-B fibers are preganglionic sympathetic neurons. Type-C fibers are located in dorsal root carrying pain/temperature and postganglionic sympathetic system. Certain types of peripheral nerves are susceptible to pressure damage (type A), hypoxic injury (type B), and local anesthesia (type C).6
The PNS consists of 12 pairs of CNs (Box 1) and 31 pairs of spinal nerves. Among the 12 CNs, olfactory nerve (Ist), optic nerve (IInd), and vestibulocochlear nerve (VIII) are pure sensory nerves; oculomotor (III), trochlear nerve (IV), abducens nerve (VI), accessory nerve (XI), and glossopharyngeal nerve (XII) are pure motor CNs; and rest are mixed. Among the spinal nerves, 8 arise from cervical, 12 from thoracic, 5 from lumbar, 5 from sacral, and 1 from coccygeal segment of spinal cord (Fig. 4).
Most spinal nerves are mixed nerves that have both motor and sensory fibers. A spinal nerve arises from the spinal cord by union of an anterior motor efferent and posterior sensory afferent. Sensory ganglion (collection of cell bodies) is located on the posterior or dorsal sensory afferent nerve. The motor efferent arises from anterior horn cell in the spinal cord and supplies motor impulses to the muscle. A motor unit is composed of anterior horn cell, peripheral nerve, neuromuscular junction, and the muscle fibers supplied by it (Fig. 5).
Clinical relevance:
- Injury to peripheral nerve can involve both axon and myelin (neurotmesis), only axon (axonotmesis), or could spare both (neuropraxia—transient nerve compression). Neuropraxia has better chances of recovery than axonotmesis and neurotmesis.
- If only one peripheral nerve is affected, it is called mononeuropathy. If more than one noncontiguous nerves are involved, it is called mononeuritis multiplex. When multiple peripheral nerves are affected, it is called polyneuropathy. Majority of systemic diseases result in polyneuropathy or mononeuritis multiplex.
- Guillain–Barré syndrome is a polyneuropathy. If it damages the myelin, it is called demyelinating polyneuropathy [acute inflammatory demyelinating polyneuropathy (AIDP)]. If it damages axons as well, it is called axonal polyneuropathy [acute motor axonal polyneuropathy (AMAN) or acute motor-sensory axonal polyneuropathy (AMSAN)].
- Nerve conduction study can study only large diameter and fast conducting nerve fibers (type A). Injury to type B and type C fibers may result in clinical symptoms of neuropathy but nerve conduction study may be normal. Hence, patients with small fiber neuropathy can have normal nerve conduction study.
- Weakness that results from lesion in the motor unit is called neuromuscular weakness. Neuromuscular diseases can be classified depending on the site of lesion as neuronopathies (anterior horn cell involvement), neuropathies (peripheral nerve disease), neuromuscular transmission disorder (myasthenic syndromes), or myopathies (muscle involvement).
CENTRAL NERVOUS SYSTEM
The CNS consists of brain and spinal cord. Brain consists of cerebrum, diencephalon, brainstem, and cerebellum. Cerebrum consists of two cerebral hemispheres and basal ganglia. Diencephalon consists of thalamus, hypothalamus, metathalamus, epithalamus, and subthalamus. Brainstem consists of midbrain, pons, and medulla (Fig. 6).
The brain and spinal cord have gray matter where cell bodies of neurons are located, and their axons constitute the white matter. Gray matter is peripherally located, and white matter is centrally located in the brain, and the reverse in the spinal cord. Both brain and spinal cord are covered by meninges and are suspended in cerebrospinal fluid. Meninges consist of dura mater, arachnoid mater, and pia mater (outermost layer to innermost layer). The inner two layers (pia mater and arachnoid mater) are called leptomeninges. The space between the two is called the subarachnoid space that contains cerebrospinal fluid. In meningitis, there is leptomeningeal enhancement that is evident on contrast neuroimaging. Dura mater is also called pachymeninges.
Spinal Cord
Spinal cord is located inside the vertebral column, occupying its upper two-third. The cord is shorter than vertebral column and ends at L1 vertebral level. It continues caudally from the medulla and ends in a conical structure called conus medullaris.
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The conus medullaris continues as a thin filament called filum terminale. The spinal cord is segmented into 31 spinal segments; and from each segment, a pair of spinal nerves arises on both the sides. Spinal segment always arises above the corresponding vertebral body level. Below the level of L1 spinal segment, the spinal nerve roots descend vertically to form a tuft, called as cauda equina (Fig. 7) due to its similarity to a horse tail.
Cross section of spinal cord is composed of inner core of gray matter with surrounding white matter. Gray matter projects into anterior, posterior, and lateral horn. White matter has dorsal, lateral, and ventral funiculus (Fig. 8). Anterior and posterior spinal nerve roots pass from spinal cord to the level of vertebral foramina where they unite to form a spinal nerve. The level of spinal nerve and vertebral levels are depicted in Table 1. Each spinal nerve is a mixed nerve, consisting of motor and sensory fibers. Once they exit vertebral foramina, they divide into anterior and posterior ramus. Posterior ramus supplies the muscles of the back and anterior ramus continues anteriorly to supply the appendicular muscles. Ascending (toward brain) and descending (from brain) tracts of spinal cord are summarized in Table 2 and Figure 9. Spinal cord is supplied by anterior spinal artery (ASA) and a pair of posterior spinal artery.
Spinothalamic tract carrying sensation to sensory cortex via thalamus includes anterior and lateral spinothalamic tract. Anterior spinothalamic tract carries light touch and pressure; it crosses over to contralateral side after ascending for 1–2 segments.9
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Lateral spinothalamic tract carrying pain and temperature crosses over immediately to contralateral side. If there is loss of light touch sensation at L2-L3 dermatome on right side, it is possible that lesion in spinal cord could be at the level of L1-L2 (left side).
Dorsal column carrying discriminative touch, vibration sensation, and proprioception ascends at the same level and on the same side till medulla and then crosses over at medullary level.
The corticospinal tract controls skilled motor activity. The lateral corticospinal tract descends and crosses over at the level of medulla to supply the contralateral side of the body. In contrast, the anterior corticospinal tract descends uncrossed till the level of spinal cord, where it crosses to supply the contralateral side. Hence, corticospinal tracts will always control the movement of opposite side of the body. Reticulospinal tract has cortical control of voluntary motor function. Rubrospinal tract facilitates flexors and inhibits the extensors. In contrast, vestibulospinal tracts facilitate the extensors and inhibit the flexors for balance control.10
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Clinical relevance:
- Spinal cord ends at L1-L2. Hence, spinal cord is shorter than vertebral column. Table 1 helps us to determine the site of vertebral level that corresponds to the given spinal cord level. Hence, if there is a lesion clinically compatible with L1-L2 spinal level, then the corresponding vertebra would be T10.
- Sensory dermatome helps in localization: A rough guide to key landmarks is given in Table 3. T10 corresponds to umbilicus—L1: groin; L2: upper medial thigh; L3: lateral lower thigh; L4: medial upper leg; L5: lateral lower leg; S1: foot; S4-S5: perianal area (Fig. 10). Hence, if there is a loss of sensation in the leg with preserved sensations at the thigh region, we know the lesion has to be below L4 (lateral lower thigh is supplied by L4 which is intact), either L5-S1 or below.
- Root value of deep tendon reflex (DTR) is useful to determine the site of lesion. Commonly elicited DTRs (with root values) are—knee jerk (L2-L4), ankle jerk (L5-S1), biceps (C5-C6), brachioradialis (C5-C6), and triceps (C7-C8). DTRs are usually lost at the level of the lesion and are exaggerated below that level.
- Similarly, superficial reflexes are useful in localization, as they are absent or hypoactive below the site of lesion and are preserved above it. Root value of superficial reflexes include—abdominal reflex [T6-T10 (above umbilicus); T10-L1 (below umbilicus)], cremasteric reflex (L1-L2), plantar reflex (L5-S1), and anal reflex (S4-S5). For example, a lesion at L2-L4 level would result in loss of knee DTRs, preserved abdominal reflex, and absent anal reflex. Similarly, a lesion at L5-S1 would result in loss of ankle DTRs and mute or absent plantar reflex.
- Any lesion at spinal cord level will result in LMN signs (loss of DTR, flaccid weakness, and fasciculation) at that level and UMN signs (spasticity and brisk DTR) below that level. Hence, lesion at L5-S1 would result in loss of ankle reflex (L5-S1 root value). L2, L3, and L4 will result in loss of knee reflex (L2-L4 root value) and brisk ankle reflex.
- Muscle power testing is useful to determine the severity of weakness (plegia versus paresis). Overall, one can remember that majority of leg and foot muscles are supplied by L4-L5-S1. Hip flexors L1-L2; thigh adductors: L2-L3; knee extensors: L3-L4; ankle dorsiflexors: L4-L5; ankle plantar flexion: S1-S2; hip extensor; and abductors: L5-S1.
- If there is a hemisection of spinal cord at one spinal level, there will be spastic paralysis on the same side below that spinal level (descending motor tracts of spinal cord supply same side), loss of joint position sensation and vibration on the same side below that spinal segment (posterior or dorsal columns ascend on the same side), and loss of pain and temperature on the contralateral side (lateral spinothalamic tract lesion cross to the opposite side). This clinical syndrome of hemisection is called Brown–Sequard syndrome.
- If the patient has loss of pain and temperature sensation (lesion of lateral spinothalamic tract) but preserved sensation of vibration and joint position (posterior columns are spared), then the lesion is affecting the center of spinal cord and sparing the dorsal aspect. This dissociated sensory loss is characteristic of conditions like syringomyelia.
- If the patient has isolated loss of joint position and vibration sensation and starts swaying with closed eyes (Romberg sign), then it indicates posterior column involvement as in vitamin B12 deficiency. To maintain a balance while standing, intact proprioception, vestibular function, and vision are required. In dorsal column lesion, proprioception is impaired, which results in swaying while standing that becomes evident once the vision is blocked by asking the patient to close his eyes.
- Loss of perianal sensation is observed in cauda equina/conus medullaris syndrome. In such situation, if there is early bladder involvement with minimal muscle weakness of lower limb, it favors conus medullaris syndrome. However, if a patient with loss of perianal sensation has severe radicular pain and spastic weakness of lower limb, it favors cauda equina syndrome.12
Table 4 Localization of lesion based on clinical case vignettes. Case scenario (clinical findings)Possible anatomical site of localizationRight lower limb weakness, tingling and numbness, radicular pain (right), areflexia, and mute plantars on right sideNerve root (radiculopathy) or plexopathy (lumbar plexus) on right sideIsolated right foot drop, atrophy of right foot muscles, especially extensor digitorum brevis (EDB), absent ankle reflex, preserved knee jerk, and mute plantar (right)Right common peroneal nerve injury (peripheral nerve involvement)Flaccid paraparesis, areflexia, mute plantars (bilateral), and presence of fasciculationsAnterior horn cell involvement (e.g., poliomyelitis)Spastic paraparesis, brisk DTRs, and extensor plantarsSpinal cord involvement, e.g., transverse myelitisParaparesis with positive Romberg signPosterior column involvement (e.g., vitamin B12 deficiency)Weakness (proximal hip girdle predominant) with hyporeflexia and muscle painMyopathy (inflammatory) (e.g., viral myositis)Proximal hip girdle weakness with associated ptosis and diurnal variation of weaknessNeuromuscular weakness, e.g., myasthenia gravis(DTRs: deep tendon reflexes) - Pain in a child with paraparesis can provide a lot of clues. Pain could be radicular, neuropathic, or nociceptive.
- Radicular pain (radiculopathy) starts from the back, radiates down the leg, and worsens with Valsalva or leg raising test. This is typically observed in compressive myelopathy secondary to vertebral involvement resulting in stretching of nerve radicals. Such radicular pain is also observed in vertebral disk prolapse with resultant compression or polyradiculoneuropathy (Guillain–Barré syndrome). This needs to be differentiated from neuropathic or nociceptive pain, which indicates a peripheral rather than cord pathology.
- Neuropathic pain is distal, severe, and burning pain with no radiation and no worsening with Valsalva/crying. It results from lesion in the peripheral nerves and nerve roots.
- Nociceptive pain results from pain receptors in skin; it is dull aching, near continuous pain that is relieved with analgesics. UMN lesions never result in neuropathic or nociceptive pain.
Table 4 provides few clinical case scenarios to understand these basic principles of localization of lesion in the spinal cord.
Brainstem
Brainstem consists of three main structures—midbrain, pons, and medulla. It hosts all the CN nuclei and other vital autonomic functions. Brainstem regulates vital cardiac and respiratory functions.
- Midbrain is known to play a role in the vision (Edinger–Westphal nucleus). It also hosts reticular activating system that controls sleep and wakefulness. Site for temperature regulation is also governed by the midbrain.
- Pons communicates signals from cerebellum to brain, it hosts vital respiratory centers as well center for bladder control (pontine micturition center).
Cranial nerve nuclei and their fibers are classified into afferent fibers and efferent fibers. Types of fiber and functions of CN nuclei are enumerated in Table 5. There are twelve pairs of CN, 10 of which arise from brainstem (Table 6). First CN (olfactory nerve) arises from olfactory mucosa and reaches the brain through cribriform plate; second CN (optic nerve) arises from the optic disc to end at optic chiasma. CN nuclei are in midbrain (III and IV CNs), pons (V, VI, VII, and VIII CNs), and medulla (IX, X, XI, and XII CNs). Each pair of CN nuclei in the brainstem supplies ipsilateral muscles of head and neck.
Blood supply of midbrain is posterior cerebral artery; pons is supplied by basilar artery (midline) and anterior inferior cerebellar artery (AICA) (lateral); and medulla is supplied by ASA (midline part of medulla) and posterior inferior cerebellar artery (PICA) (lateral medulla) (Fig. 11).
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Clinical relevance: Brainstem can be broadly divided into midline and lateral sides. The structures that are in midline include CN III, IV, VI, and XII. Midline tracts also include medial longitudinal fasciculus (MLF), motor tract (corticospinal tract), and medial lemniscus (contralateral vibration and proprioception) (all start with letter M are midline). Hence, a midline lesion of the pons on the right side would affect right sixth CN nucleus (impaired abduction of right eye), right MLF (impaired adduction of left eye), and right corticospinal tract (left hemiparesis). This may occur secondary to top of basilar artery syndrome where basilar artery that supplies the midline part of pons is affected.
Structures that are present laterally include CN V, VII, IX, and XI. Lateral columns include sympathetic tract and spinothalamic tract (both start with letter S are inside). Hence, a right lateral pontine infarct would affect right VIIth CN nucleus (right facial palsy), right spinothalamic tract (loss of pain and temperature sensation on the left side), and right fifth CN nucleus (loss of facial sensation on the right side).
Fig. 11: Blood supply of brainstem. (AICA: anterior inferior cerebellar artery; ASA: anterior spinal artery; PCA: posterior cerebral artery; PICA: posterior inferior cerebellar artery)
Clinical features of various brainstem syndromes are summarized in Table 7.
Cerebellum
Cerebellum is connected to brainstem by superior, middle, and inferior cerebellar peduncle. Inputs to cerebellum reach via middle and inferior cerebellar peduncle. Efferents from cerebellum leave via superior cerebellar peduncle. Cerebellum is composed of vermis in the midline, two cerebellar hemispheres and a flocculonodular lobe (Fig. 12). Vermis controls the truncal stability and proximal limb movement; whereas, cerebellar hemispheres control the distal limb movement. Cerebellum modifies motor command of corticospinal pathway to make the movement smooth, adaptive, and accurate. Main functions of cerebellum include maintenance of posture and balance, coordination of voluntary movement, and motor learning (learning new motor movements with trial and error).
Anatomically, cerebellum has two parts—cerebellar cortex (neurons) and cerebellar deep nucleus (output). There are three deep nuclei of cerebellum:
- Fastigial nucleus
- Interpositus nucleus (emboliform and globose nucleus)
- Dentate nucleus (projects to contralateral red nucleus and ventrolateral thalamus)
Clinical relevance:
- Midline cerebellar dysfunction leads to truncal ataxia.
- Cerebellar hemispheric lesions lead to limb ataxia, dysmetria, dysdiadochokinesia, intentional tremors, dysarthria, and hypotonia.15
Table 7 Brainstem syndromes. LevelStructure involvedClinical findingMidbrain (medial)(Benedict syndrome)- CN III
- Medial lemniscus
- Red nucleus
- Oculomotor palsy
- C/L loss of posterior sensation
- Tremor/ataxia
Midbrain (peduncle)Weber syndrome- CN III
- Corticospinal
- Corticobulbar
- Oculomotor palsy
- C/L hemiparesis
- Pseudobulbar palsy (spastic dysarthria)
Pons (medial)- Corticospinal
- VI CN
- VII CN
- MLF, VI CN
- C/L hemiparesis
- I/L VI CN palsy
- I/L VII CN palsy
- Lateral gaze restriction
Pons (lateral)- Vestibular nucleus
- Spinothalamic tract
- V CN
- VII CN
- Sympathetic
- Vertigo/ataxia
- C/L pain and temperature loss
- I/L loss of facial sensation
- I/L VII CN palsy
- Horner syndrome
Medulla (medial)- Corticospinal
- Medial lemniscus
- XII CN
- C/L hemiparesis
- C/L loss of posterior column sign
- XII CN palsy
Medulla (lateral)- Vestibular nucleus
- Spinothalamic tract
- V CN
- Sympathetic tract
- Vertigo/ataxia
- I/L pain and temperature loss
- C/L loss of facial sensation
- Horner syndrome
(CN: cranial nerve; I/L: ipsilateral; C/L: contralateral) - Involvement of flocculonodular lobe results in nystagmus and ocular movement disorders.
Diencephalon
Diencephalon is the structure between brainstem and cerebrum. It consists of thalamus, metathalamus, epithalamus, subthalamus, 16and hypothalamus. Thalamus acts as a sensory relay station for all sensations of the body except olfactory system. All sensations such as pain, touch, and temperature from the limbs ascend the spinal cord to be relayed to parietal cortex through thalamus. Similarly, auditory sensations from medial geniculate nucleus relay through thalamus to auditory cortex. Thalamus also regulates consciousness and emotional content.
Clinical relevance: Thalamic syndromes are characterized by variable clinical presentations including loss of sensation in the limbs, ocular motility deficits, visual processing defects, memory problems, alteration of sensorium, or auditory problems. Thalamic lesions in children result in movement disorders including dystonia, myoclonus, athetoid movements, or tremors. Hence, there is a wide variation in neurological manifestations of thalamic lesion depending on the thalamic nucleus that is affected.
Basal Ganglia
Basal ganglia are a set of gray matter nuclei, which consist of caudate, putamen, globus pallidus, subthalamic nucleus, substantia nigra (SN), and ventral tegmentum (Fig. 13). Corpus striatum is a term used to denote head of caudate plus putamen. Lentiform nucleus consists of putamen and globus pallidus. Functions of basal ganglia are complex. They constitute extrapyramidal system that controls movement. In addition, basal ganglia have role in emotion, memory, and cognitive functions. Dysfunction of basal ganglia results in movement disorders. The basal ganglia circuit is complex, and it is difficult to clinically localize different types of movement disorders.
Basic concept in regulation is that reduced inhibition will increase output and increased inhibition will decrease the output. There is a direct and an indirect pathway (Fig. 14). Direct pathway stimulates the muscle movement and indirect pathway inhibits the muscle movement. Globus pallidus internus is the main output of basal ganglia that is inhibitory to thalamus thus to the cortex. When patient wants to move a limb, the cortex stimulates the putamen, which in turn inhibits GPi, thus reducing the inhibition of GPi on thalamus. This in turn excites cortex to perform the movement. This pathway where putamen directly inhibits GPi is called direct pathway. The inhibitory neurotransmitters are GABA and dopamine and excitatory neurotransmitters are glutamate and dopamine. Basal ganglia pathology results in increased inhibition of GPi, thus decreasing its inhibition on thalamus, resulting in increased movements. This forms the basis for hyperkinetic movement disorders in children.
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At rest, cortex activates putamen, which in turn increases inhibition on GPe that releases inhibition on GPi. This makes GPi more active which will inhibit thalamus, thus leading to lesser excitation to motor cortex. This pathway of inhibition of GPi through GPe is called indirect pathway, which inhibits muscle movement. SN is like a hand brake of car that needs to be released when car starts moving. SN receives cortical input that we are starting movement, which stimulates direct pathway and inhibits indirect pathway at rest. Subthalamic nucleus is excitatory to GPi. Degeneration of dopaminergic nigrostriatal pathway might lead to increased inhibition of movement even when the movements are desired. This leads to hypokinetic movement disorder with Parkinsonian features (Fig. 15).
Fig. 14: Basal ganglia motor circuit. (SNr: substantia nigra pars reticulata; GPe: globus pallidus externa)
Fig. 15: Abnormalities in basal ganglia motor circuits (dark lines indicate inhibition; light lines indicate excitation); thickness of the line depicts the strength of output. (SNc: substantia nigra pars compacta; SNr: substantia nigra pars reticulata; GPe: globus pallidus externa; GPi: globus pallidus interna; STN: subthalamic nucleus; VL: ventrolateral nucleus of thalamus; PPN: pedunculopontine nucleus)
Cerebrum
Cerebrum consists of two cerebral hemispheres connected by corpus callosum. Cerebral cortex (gray matter) runs into folds called gyri and fissures in-between are called sulci. 18Based on the large sulci, cerebral cortex is divided into four lobes—frontal, temporal, parietal, and occipital. Based on the area represented in the lobe, there are various functions of these four lobes of the brain (Table 8). Frontal lobe is largely responsible for cognitive function, expressive language, and voluntary movement. Parietal lobe processes all sensory inputs like pain, temperature, pressure, and touch. Occipital lobe is responsible for processing the visual signals and temporal lobe processes the auditory signals and memory.
Consciousness
Consciousness refers to the state of awareness of self and the environment. It has two dimensions—wakefulness and awareness. Wakefulness or arousal is mediated by the ascending reticular activating system, a diffuse network of neurons originating in the tegmentum of the pons and midbrain and projecting to diencephalic and cortical structures. Awareness is dependent on the integrity of the cerebral cortex and its subcortical connections (Fig. 16).
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Clinical relevance: Consciousness is altered in lesions of reticular activating pathway in the brainstem above the mid pons level or thalamic or extensive cortical lesion. Flowchart 1 summarizes the stages of altered sensorium into conscious, minimally conscious state, vegetative state, and coma. Impaired consciousness implies a significant impairment in the awareness of self and of the environment, with variable degrees of wakefulness. Descriptive terms such as somnolence, stupor, obtundation, and lethargy used to denote different levels of consciousness are best avoided, given the lack of uniformity in the way these states are defined in the literature.
States of altered consciousness can be categorized into one of the following:
- Conscious: If the patient has preserved awareness and wakefulness (arousal), then the patient is conscious.
- Minimally conscious state: If wakefulness is preserved, but awareness is suboptimal with few meaningful and reproducible response then it is called minimally conscious state. Patient demonstrates minimal but definite behavioral evidence of self or environmental awareness. Patients in this state are able to do any or all of the following—follow simple commands, gesturally or verbally give yes–no responses (regardless of accuracy), verbalize intelligibly, or perform movements or affective behaviors in contingent relation to environmental stimuli (and not due to reflexive activity).
- Vegetative state: If wakefulness is preserved, but awareness is completely absent, then it is called vegetative state. If the same vegetative state persists for more than 30 days, it is called persistent vegetative state. It results from extensive cortical damage with preserved brainstem and reticular activating system. Patient might show signs of preserved sleep wake cycle and some behavioral arousal (like yawning and sneezing). States like akinetic mutism, coma vigil, and abulia are also often used to describe this state. These terms are best avoided.
- Coma: If both wakefulness and awareness are impaired, but brainstem reflexes (such as Doll's eye response and corneal reflex) are preserved, this state is called coma. A comatose patient has no meaningful eye opening.
- Brain death: Absence of awareness, wakefulness, and brainstem reflexes suggests brain death.
- Locked-in syndrome: If wakefulness and awareness are preserved but the patient is unable to communicate or move owing to ventral pontine lesion, this state is called locked-in syndrome. The movement or speech is locked leading to a mute and quadriplegic patient.
Language
Language is defined as use of conventional system of symbols (spoken word, sign language, written words, and pictures) for communication. It has two main components—receptive (listening and reading) and expressive (speaking and writing). Receptive component is perceived by Wernicke area in the superior temporal gyrus; whereas, expressive motor component of speech is governed by Broca area located anteriorly in inferior frontal gyrus (Fig. 17). Wernicke area is connected to Broca area through arcuate fasciculus, which governs the repetition in the language. If the repetition is preserved, receptive aphasia is called transcortical sensory aphasia and expressive aphasia is called transcortical motor aphasia. Flowchart 2 summarizes the types of aphasia based on the comprehension and repetition.
Clinical relevance:
- Dysfunction of language is called aphasia. Aphasia occurs when there is a lesion in the dominant hemisphere.
- Lesions in the anterior part of language area results in expressive aphasia, where the child omits words especially nouns and has nonfluent speech. Most children with nonfluent aphasia often have associated right hemiparesis considering the proximity of motor cortex to Broca area and left hemisphere being dominant hemisphere.
- In contrast, lesions in the posterior part of language area (stroke involving parieto-occipital cortex) results in receptive aphasia where the speech will be fluent but will have lot of word substitutions, and neologistic words making the speech incomprehensible.
- In dense middle cerebral artery (MCA) stroke of left side, all functions of language including comprehension, fluency, and repetition are affected resulting in global aphasia.
- Isolated lesion of angular gyrus results in nominal aphasia (inability to name an object).
For instance, if you are looking for an object in a dark room, you start your search, you might end up getting the right thing (or the right word), you might get something that was different from what you were searching for (neologistic words), or you might not get anything. This is what happens to an aphasic patient when commanded to respond. Hence, aphasia is inability to understand or express words for the purpose of communication, even though the primary sensorimotor pathways to receive and express language and the mental status are relatively intact.
Speech
Speech is defined as expressive production of sound that includes articulation, fluency, with voice and resonance quality. Defects of articulation are called dysarthria. Sound in the speech is produced by lips (labial), tongue (lingual), and soft palate (guttural). Syllables like “pa” are produced by lips (labial sounds), “ta” are produced by tongue (lingual sounds), and “kha” are produced by soft palate (guttural sounds). Try saying “papapapa”; you can see that sound is produced by lips. Try saying “ta-ta-ta-ta” you can feel that this sound is produced by tongue. Similarly, try saying “kha-kha-kha” you can feel that this sound is produced from the depth of throat. So, if I am able to clearly say “pa-pa-pa-ta-ta-ta-kha-kha-kha”, I know I do not any articulation problems (pa-ta-kha in Hindi is Crackers; easy to remember).
Clinical relevance: Articulation of speech is governed by cerebellum, pyramidal, and extrapyramidal pathways. Dysarthria results from disturbance in the muscular control over the speech mechanism. It could be cerebellar, spastic, or extrapyramidal dysarthria (Table 9). Dysarthria is different from dysphonia, which refers to abnormalities of voice secondary to local laryngeal abnormality.
Homunculus
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If one draws a miniature human being in the precentral gyrus (motor cortex) according to the part of the body that is represented by the area, it is called motor homunculus and if the same is drawn over the post-central gyrus (sensory cortex), it is called sensory homunculus. Cortical representation is largest for face, hands, and thumb owing to their dense innervations. Foot and leg are represented in the medial portion of cerebral cortex; whereas, hand, thumb, and face are represented in lateral cerebral cortex (Fig. 18).
Brain has two hemispheres (right and left). It is well known that right side controls the movements and sensations of the left side of the body and vice-versa. Although the functions of both sides of brain are similar, hemisphere that controls language is referred to as dominant hemisphere. In the dominant hemisphere, there is also integration of language with intellect and emotions.
Based on the type of neurons and its organization, brain is divided into 52 areas called as Brodmann areas. The important Brodmann areas include area 4 (primary motor cortex), area 17 (primary visual cortex), area 22 (primary auditory cortex), and area 44 (Broca motor speech area). These areas have been mapped in Figure 19. Functions of important areas along with features of lesion in individual areas have been outlined in Table 10.
Clinical relevance:
- In general, for right-handed and majority of left-handed people, left hemisphere is the dominant hemisphere. If stroke affects the left hemisphere, the patient will have profound involvement of speech resulting in aphasia. In contrast, right hemispheric stroke may not impair the speech profoundly although the quality of the speech may be affected.
- Majority of children with hemiparesis have predominant weakness of upper limb more than lower limb owing to larger representation of upper limb and face.23Similarly, distal weakness of upper limb is more evident as compared to proximal weakness considering larger representation of hands when compared to arm. This is applicable only in extensive cortical lesions involving the entire hemisphere.
- If a comatose patient has paucity of movement of a single lower limb, it indicates contralateral medial cortical lesion that has lower limb representation. This condition occurs in falcine herniation where a lesion in one cortical hemisphere pushes the falx cerebri toward medial side of contralateral hemisphere where the lower limb is represented.
White Matter Tracts of Cerebrum
Tracts are bundle of nerve fibers present in CNS. As discussed above, motor neuron can be UMN or LMN. UMN pathway includes—(1) corticospinal tract till it reaches the motor neuron in the spinal cord and (2) corticobulbar tract from brain to motor nuclei of CNs in the brainstem. Corticospinal and corticobulbar fibers constitute pyramidal tracts.24
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Voluntary motor function of the body and face are controlled by pyramidal tract and extrapyramidal tracts. These tracts are described below:
- Corticospinal tract: Pathway starts from cortex, travels through subcortical structures, internal capsule, midbrain, pons, and then crosses at medulla to reach motor neuron along contralateral spinal cord. Most of corticospinal fibers cross to form the lateral corticospinal tract; few remain uncrossed and enter the spinal cord as anterior corticospinal tract (Fig. 20). These pathways directly control the voluntary movement.
- Corticobulbar tract: Pathway from the cerebral cortex to ipsilateral and contralateral brainstem motor nucleus is called corticobulbar tracts. CN nuclei usually have bilateral innervation, except for a part of seventh CN that supplies lower half of the face, which has only contralateral innervation.
Extrapyramidal tracts consist of rubrospinal tracts, tectospinal tracts, reticulospinal tracts, and vestibulospinal tracts. Extrapyramidal pathway is involved in initiation of voluntary movement and selective control of agonist and antagonist group of muscles. Hence, pyramidal tract is the main performer and extrapyramidal tracts are modulators of voluntary motor activity.
Clinical relevance:
- Upper motor neuron and LMN involvement can be differentiated clinically. UMN syndrome has spasticity, brisk deep tendon reflexes, and extensor plantar response. In contrast, LMN syndrome is characterized by weakness, flaccidity, atrophy of muscles with decreased or normal deep tendon reflexes. Table 11 summarizes the clinical differentiation between UMN and LMN lesions.
- Injury to pyramidal tract will result in spastic paralysis (weakness, spasticity, and brisk deep tendon reflexes) and injury to extrapyramidal pathway would result in movement disorders like chorea, athetosis, ballismus, and dystonia.
Upper motor neuron lesion often results in spastic hemiparesis. In a child with spastic hemiparesis, the lesion could be anywhere from the cortex, subcortical structures, internal capsule, or at the level of brainstem. Following points need to be considered while localizing the UMN type of lesion:
- Cortical involvement: Presence of seizure, altered awareness, and coexistent motor and sensory deficit (as motor and sensory cortices are nearby) suggest cortical involvement.26
Table 11 Differences between upper motor neuron (UMN) and lower motor neuron (LMN) lesion. FindingUMN lesionLMN lesionWeaknessSpastic weaknessFlaccid weaknessDeep tendon reflexBriskSluggish or absentAtrophyMay or may not be presentPresentBabinski reflexExtensor responseFlexor responseFasciculations/fibrillationAbsentFasciculation present in anterior horn cell involvement; fibrillation in muscle involvementInvolvement of frontal eye field (in frontal region of same side) will result in eye deviation to same side (eyes deviate toward destructive lesion). Hence, if there is a block in superior division of left MCA, it will involve left motor cortex, sensory cortex, inferior frontal gyrus (that lodges Broca area of speech), and frontal eye field. This will result in right hemiparesis, hemisensory loss on right side, Broca aphasia, and eyes being deviated to left side. - Internal capsule: Internal capsule has five parts—anterior limb, genu, posterior limb, sublentiform (carries auditory fibers), and retrolentiform (carries visual fibers) (Fig. 21). Sensory fibers from thalamus to cortex called thalamic radiations traverse through both anterior and posterior limb of internal capsule. Genu of internal capsule has corticobulbar tract and posterior limb has corticospinal tract (Fig. 21). Internal capsule is supplied by lenticulostriate branch of MCA (superiorly) and recurrent artery of Huebner, a branch of anterior cerebral artery (ACA) (inferiorly in the anterior limb and genu) and anterior choroidal artery, a branch of internal carotid artery (inferiorly in posterior limb). A lesion in internal capsule will result in one or more of the following—hemiplegia (corticospinal tract involvement), hemisensory loss (thalamic radiation involvement), and CN palsy (corticobulbar fibers). Since the fibers for arm, trunk, and legs are closely packed, it results in dense hemiplegia involving both arms and legs equally. This is in contrast to cortical lesion where upper limb (which has a larger representation in the cortex) is involved more compared to lower limb. A lenticulostriate artery stroke on the right side can result in left-sided dense hemiplegia with right UMN type of facial palsy. The sensory tracts of posterior limb are often supplied by anterior choroidal artery and hence may be spared completely in lenticulostriate artery stroke. Involvement of lenticulostriate artery is common in adults with chronic hypertension or diabetes mellitus.
- Brainstem: Most of brainstem syndromes are crossed. This is obvious as CNs descend along same side whereas corticospinal tract will decussate at the level of medulla to supply opposite side of the body. Depending on CN involvement, lesion can be localized to midbrain (III or IV CN), pons (V, VI, VII, or VIII CN) or medulla (IX, X, XI, or XII CN).
BLOOD SUPPLY OF BRAIN
Arterial supply consists of anterior circulation (internal carotid artery) and posterior circulation (vertebral artery). Internal carotid artery divides into anterior and middle cerebral artery (MCA). MCA divides into superior and inferior division. Anterior communicating artery connects right and left ACA. Two vertebral arteries join at the level of pons to form basilar artery that subsequently divides into two posterior cerebral arteries. Posterior communicating artery connects posterior cerebral artery with MCA and is a branch of internal carotid artery.
Circle of Willis is formed by terminal portion of internal carotid artery, proximal portion of ACA, anterior communicating artery, posterior communicating artery, and proximal portion of posterior cerebral artery (Fig. 22). Vertebral artery has two branches—ASA and PICA. Branches from the basilar artery include superior cerebellar artery and AICA.
Anterior cerebral artery supplies anteromedial portion of brain, MCA supplies the lateral surface of brain, and posterior cerebral artery supplies both medial and lateral surface of posterior portion of brain (Fig. 23). ACA through its medial lenticulostriate artery supplies medial basal ganglia, corpus callosum, and genu of internal capsule. Table 12 summarizes the blood supply of various basal ganglia structures.
Clinical relevance:
- Anterior cerebral artery infarct results in weakness of contralateral lower extremity, gait apraxia, and urinary incontinence, as ACA supplies medial portion of the brain where legs are represented in the motor homunculus. Frontal lobe (supplied by ACA) may result in gait apraxia. Similarly, cortical control of bladder is governed by frontal lobe. Urinary incontinence in socially inappropriate situations is observed in frontal lobe lesion (ACA infarct). (Apraxia means inability to perform a learned skilled action despite normal motor, sensory, and cerebellar functions.)
- Middle cerebral artery supplies sensorimotor cortex except for lower extremity. Hence, a patient with dense MCA stroke would have contralateral motor weakness (affecting face and upper limb considering its cortical representation), sensory loss, homonymous hemianopia, along with aphasia (dominant hemisphere), and hemineglect (nondominant hemispheric lesion).
- Posterior cerebral artery supplies thalamus and temporo-occipital cortex. Most common presentation is visual field defect (homonymous hemianopia) with cortical lesion (area 17). Brainstem lesion would often result in alteration of sensorium (reticular activating system in brainstem is responsible for wakefulness) and multiple CN palsies (CNs emerge at the level of brainstem). More examples are provided in Chapter 30.28
Venous Drainage of Brain
Venous drainage of brain can be divided into superficial venous system and deep venous system. Superficial venous system consists of superior cerebral veins, middle (superficial), and inferior cerebral veins. The two important veins in superficial venous system are superior anastomotic vein of Trolard (connects superior sagittal sinus to superficial middle cerebral vein) and inferior anastomotic vein of Labbe (connects superficial middle cerebral vein to transverse sinus). Superficial venous system especially superior sagittal sinus drains the entire cortex. Lateral sinus including transverse sinus and sigmoid sinus drains cerebellum, brainstem, and posterior regions of cortex. Inferior sagittal sinus drains into straight sinus that joins the confluence of sinuses along with superior sagittal sinus and a pair of transverse sinuses. Transverse sinus continues on each side to form sigmoid sinus that ultimately drains into internal jugular vein.
Thalamostriate vein and choroidal vein join to form internal cerebral vein, which 29joins basal vein of Rosenthal to form great cerebral vein. The great cerebral vein (vein of Galen) drains into straight sinus (Fig. 24). Deep venous system drains cerebellum, brainstem, and posterior regions of cortex. Deep white matter and basal ganglia are also drained by deep venous system.
Clinical relevance:
- In contrast to arterial stroke, venous strokes do not have any clinical localization considering extensive collaterals between various venous channels. Among the superficial and deep venous system, superior sagittal sinus is the most common site of thrombosis in children.
30Table 12 Blood supply of basal ganglia. Area of brainBlood supplyBasal gangliaHead of caudateRecurrent branch of ACARest of caudate and putamenPenetrating branches of MCAGlobus pallidusAnterior choroidal arteryThalamusPosterior cerebral artery and posterior communicating arteryAnterior limb of internal capsule and genu- Lenticulostriate branch of MCA
- Recurrent branch of ACA
Posterior limb of internal capsule- Lenticulostriate branch of MCA
- Anterior choroidal branch of ICA
(ACA: anterior cerebral artery; MCA: middle cerebral artery) - Since venous collaterals are well formed, majority of patients with venous thromboses have insidious onset of symptoms in contrast to sudden onset of focal deficit in arterial stroke.
- Children with venous stroke often present with features of raised intracranial pressure (headache, vomiting, irritability, or alteration of sensorium) and seizures. Motor deficits are more common in arterial stroke in comparison to venous stroke.
- Since capillaries and veins are fragile, venous stroke often have hemorrhage. Hence, in presence of intraparenchymal hemorrhagic infarct, one must always consider venous thrombosis especially when there are predisposing risk factors like diarrheal dehydration, severe anemia, postoperative period, or any underlying cyanotic congenital heart disease.
- Venous sinus thrombosis is best picked up in magnetic resonance venography, which may demonstrate nonvisualization of the sinus, flow defect, and presence of collaterals.
CEREBROSPINAL FLUID
Cerebrospinal fluid (CSF) is formed by choroid plexus located in walls of lateral ventricle. CSF flows from lateral ventricle to third ventricle through foramen of Monro. It then passes through aqueduct of Sylvius to the fourth ventricle, and via foramen of Luschka and foramen of Magendie and ultimately drains into the basal cisterns and subarachnoid space (Fig. 25). CSF from subarachnoid space flows over the surface of brain parenchyma to be finally drained into venous circulation (superior sagittal sinus). Arachnoid granulations are considered as main site for CSF reabsorption. CSF is produced at the rate of approximately 500 mL/day. CSF has lower protein, glucose, and potassium than plasma but higher chloride. It acts as a cushion to brain and spinal cord.
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Clinical relevance: Enlargement of ventricles (ventriculomegaly) can result from accumulation of CSF resulting in hydrocephalus. Hydrocephalus can be communicating or noncommunicating. If lateral ventricle, third ventricle, and fourth ventricle are all dilated, it would be considered as communicating hydrocephalus. However, if only lateral and/or third ventricle are dilated, and fourth ventricle is normal, it would be considered as noncommunicating hydrocephalus.
MENINGES
Meninges consist of pia mater, arachnoid mater, and dura mater (P-A-D). Pia mater is a vascular structure closely adherent to the surface of brain. Dura mater lies against the bone with thick connective tissue and contains the venous sinuses. There are two layers of dura mater—periosteal layer attached to skull bone and the meningeal layer. Space between these two layers has venous sinuses. Space between periosteal layer of dura mater and skull is called extradural space. Space between dura mater and arachnoid mater is called subdural space. Cerebrospinal fluid lies in the subarachnoid space between arachnoid mater and pia mater. Pia mater is very closely stuck to the brain. Falx cerebri is dura mater that dips in-between the cerebral hemisphere. Dura mater that separates cerebellum from overlying cerebral surface is called tentorium cerebelli (Fig. 26).
SPECIAL SENSES AND THEIR NEURAL PATHWAY
Special senses include smell, vision, sound or hearing, balance and taste. Olfactory system transmits the sense of smell from olfactory epithelium to olfactory cortex through olfactory nerve (first CN).
Auditory pathway starts from cochlea, cochlear nerve, cochlear nucleus, trapezoid body, lateral lemniscus, inferior colliculus, medial geniculate body, and auditory radiation, and it ends at auditory cortex. Vestibular nucleus in brainstem receives signals from vestibular receptors in labyrinth (utricle and saccule). Vestibular nucleus is responsible for maintenance of balance and posture.
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The visual pathway is discussed in detail below.
Visual Pathway
Visual pathway consists of retina, optic nerve, optic chiasma, optic tract, lateral geniculate body, optic radiations, and visual cortex (Fig. 27). Optic nerve is a sensory nerve that is covered by meninges rather than neurilemma. Hence, optic nerve does not regenerate when cut. It lies in close relation to the sphenoid sinus, which accounts for retrobulbar neuritis among children with sphenoid sinus infection. Optic chiasma lies over the pituitary (Sella turcica) leading to visual field defect in lesions of pituitary like adenoma. Lesions along the optic pathway can be determined by testing field of vision.
Clinical relevance:
- Optic nerve lesion: Lesions of optic nerve result in ipsilateral blindness with loss of direct as well as consensual light reflex (observed in unaffected eye) on the same side. Direct light reflex will be preserved in other eye and consensual reflex of other eye can be observed in affected side. Accommodation reflex is preserved in optic nerve lesion.
- Optic atrophy: There are two types of optic atrophy. Primary optic atrophy results in chalky white optic disk with well-defined margins. Secondary optic atrophy results as a sequelae of previous papilledema, which is seen as blurred disk margins with peripapillary sheathing and tortuous veins.
- Lesion at optic chiasma (tumors of pituitary gland, suprasellar aneurysm) results in bitemporal hemianopia. Lateral chiasmal lesion (distention of 3rd ventricle) is characterized by binasal hemianopia.
- Optic tract lesion results in homonymous hemianopia, whereas lesions in occipital lobe cortical lesion result in homonymous hemianopia with macular sparing.
- Parietal lobe lesion results in inferior quadrantanopia hemianopia, whereas temporal lobe lesion results in upper quadrantanopic hemianopia.
Ocular Reflexes
Light Reflex
Light reflex is mediated via fibers from optic tract to pretectal nucleus to Edinger–Westphal nucleus (EWN) located in the midbrain. Fibers from optic tract enter brachium of superior colliculus instead of lateral geniculate body (Fig. 28A). Fibers from EWN enter ciliary ganglion and supply the ciliary muscles causing pupillary constriction. Pathway for light reflex does not pass through occipital cortex. Hence, children with cortical blindness will have vision loss with preserved pupil light reflex.
Accommodation Reflex
Accommodation reflex is mediated via occipital cortex.
Fibers from optic tract reach lateral geniculate nucleus, which in turn relays signals to occipital visual cortex. Signals from visual cortex, reach pretectal area to ultimately relay to EWN (ciliary muscles cause pupillary constriction and thickening of lens) and prefrontal cortex (convergence through frontal eye field and area 8 [not shown in figure]) (Fig. 28B). Accommodation involving convergence and pupillary constriction to focus on a nearby object requires intact visual cortex.
Abnormalities in Pupil
Normally, pupils are normally equal in size, round, centered in iris and react to direct and consensual light reflex. There are various abnormalities of pupil (Table 13).
Ocular Motility
Extraocular Muscle Innervation
Monocular eye movements are called ductions (abduction and adduction). Binocular conjugate eye movements are called version (right or left sided version). Disconjugate eye movements are called vergences. Convergence is movement of both eyes nasally and divergence is movement of both eyes temporally.
We know that 4th nerve supplies superior oblique [SO supplied by 4, can be remembered as SO4 (sulphate)] and 6th nerve supplies lateral rectus (LR6). Rest of extraocular muscles, levator palpebrae superioris, and sphincter papillae are supplied by 3rd CN. Hence, complete third CN palsy will result in:
- Bilateral or unilateral ptosis (LPS involvement)
- Pupils are dilated and nonreactive to light and accommodation
- Eye movements are restricted to lateral gaze; eyes are turned out and down
Ptosis may result from 3rd CN palsy or weakness of tarsal muscles (due to sympathetic involvement) but in the latter, lid can be raised voluntarily.34
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Most common cause of unilateral complete ptosis is 3rd CN palsy. The most common cause of unilateral partial ptosis is Horner's syndrome and bilateral mild ptosis is myasthenia gravis and other neuromuscular causes. Ptosis can be congenital or acquired. In congenital ptosis, LPS is fibrosed, leading to lid lag on downgaze.35
Squint or Strabismus
Deviation of eye, which is otherwise not appreciable but manifests on cover–uncover test, is considered latent squint (phoria). When the deviation is obvious on primary gaze, it is called tropia: eyes deviated laterally (exotropia), eyes deviated medially (esotropia), eyes deviated upward (hypertropia), and eyes deviated downward (hypotropia).
When normal eye is fixing, the deviation that occurs in affected eye is called primary deviation. On covering the normal eye, when affected eye starts fixing, the movement of normal eye under the cover is called secondary deviation. When secondary deviation is more than primary deviation, it is called paralytic squint.
Broadly, there are two main types of strabismus—concomitant squint and paralytic squint. When the misaligned eye maintains its abnormal position in all direction of gaze, it is called concomitant squint. Hence, in right eye exotropia, in primary position, right eye is deviated out and it remains deviated out when moved right, left, upward, or downward. Whereas, if there is paralytic squint in right eye (right exotropia), in primary gaze, eyes are deviated to right. When patient is asked to look right, his eyes will move to right, when asked to look left, his eyes will not move, when asked to move up, his eyes will move up and out, and when asked to look down, it will move down and out. Hence, in paralytic squint, deviation is more evident in one gaze when compared to other gaze, whereas in concomitant squint, deviation is same in all gaze.
Clinical relevance:
- Paralytic squint, as the name suggests, results from CN palsy (3rd, 4th, or 6th CN) whereas concomitant squint usually have no definitive etiology.
- Face turn, head tilt, and chin lift will be seen in paralytic squint.
- Similarly, diplopia or double vision will be a complaint in paralytic squint and not in concomitant squint.
Ophthalmoplegia
Ophthalmoplegia refers to inability to move eye muscles. When paralysis involves pupillary and ciliary muscles, it is called internal ophthalmoplegia. When paralysis involves extraocular muscles alone, it is called external ophthalmoplegia.
Supranuclear Control of Eye Movement
Supranuclear control of eye movements are summarized in Table 14. Pathways involved in the supranuclear control of saccadic movements are depicted in Figure 29. Left-sided cortex stimulates right parapontine reticular formation (PPRF), which in turn stimulates right-sided 6th CN (moving the right eye to look right) and through MLF also stimulates the left 3rd CN (moving the left eye to look at right). Hence, normally left cortex will cause conjugate deviation of eyes toward the right. Types of lesions that can occur in this pathway include:
- Lesion at right 6th CN: Right eye cannot look toward the right but can look in all other direction and left eye can look in all directions. The only restriction is abduction of right eye. This indicates isolated right 6th CN palsy.
- Lesion in right PPRF: We know that right PPRF is responsible for stimulating the right 6th nerve and through MLF it will stimulate the left 3rd nerve. If there is right PPRF lesion, right 6th nerve and left 3rd nerve will not be stimulated. Hence, there will be a right-sided gaze palsy (neither right eye nor left eye can look toward right). But, right cortex continues to stimulate left PPRF forcing the eyes to look toward left. Hence, the eyes are tonically deviated to the opposite side with PPRF lesion.
- Lesion at left MLF: With left MLF lesion, there is disconnection between right PPRF and left 3rd CN nucleus. When stimulated, right PPRF will command right eye to look right but cannot command the left eye to look right owing to left MLF lesion. Hence, when patient is asked to look toward the right side, right eye abducts (and also has nystagmus) and left eye has no movement. When asked toward left, left eye will abduct and right eye will adduct, which is normal. This lesion is called internuclear ophthalmoplegia (INO).
- Lesion involves both MLF: Bilateral MLF lesion will disconnect both PPRF to contralateral 3rd CN nucleus. Hence, when patient is asked to look at either side, the abducting eye moves but adducting eye does not move. This results in lack of bilateral adduction.
- Lesion involves right PPRF and both MLF: If there is a lesion in right PPRF, there will be right gaze palsy. In addition, if there is bilateral MLF lesion as well, there will be no adduction in both the eyes. This results in no adduction in both eye and no abduction in right eye. Hence, only left eye can abduct, rest of three movements (abduction of right eye and adduction of right and left eye) are not possible (so, three out of four movements are restricted: 1½). This is called one and half syndrome.
- Lesion at cortex: Left-sided destructive lesion will result in no signal to right PPRF. Right cortex will stimulate left PPRF to look at left. Hence destructive cortical lesion will result in eye deviated to same side. In contrast, irritative cortical lesion will hyperstimulate contralateral PPRF. Hence, eye looks toward destructive cortical lesion and looks away from irritative cortical lesion.
Common Abnormal Eye Movement
The common abnormal eye movements include opsoclonus, ocular dysmetria, ocular flutter, ocular bobbing, and ocular myoclonus (Table 15).37
Limbic System
Limbic system in brain is responsible for emotional behavior, memory formation, olfaction, and control of food habits. It is composed mainly of hypothalamus, hippocampus, amygdala, limbic cortex (cingulated gyrus and parahippocampal gyrus), olfactory bulb, and septal area (Fig. 30). Spatial memory is governed by parahippocampal gyrus, whereas, long-term memory by hippocampus. Amygdala controls aggression, anxiety, emotional memory, and social cognition. Hence, a lesion in amygdala would result in docile behavior, hypersexuality, and compulsive attentiveness (Kluver–Bucy syndrome). Cingulate gyrus controls autonomic function regarding heart rate and blood pressure.
Papez postulated that a circuit linking consciousness, thought, and emotion involves hippocampal formation, cingulated gyrus, mammillary body (hypothalamus), and anterior nucleus of thalamus (Papez circuit) (Flowchart 3). The structures involved in memory are summarized in Table 16.
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Flowchart 3: Papez circuit showing the link among hypothalamus, anterior thalamus, cingulated cortex, and hippocampus.
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AUTONOMIC NERVOUS SYSTEM
It consists of sympathetic and parasympathetic nervous system. Sympathetic nervous system has thoracolumbar origin (T1 to L3-L4) and parasympathetic nervous system has craniosacral origin [CN 3, 7, 9, and 10 and sacral (S2-S4)]. Autonomic nervous system has noradrenergic neurons and cholinergic neurons. In autonomic nervous system, motor neurons are categorized into preganglionic neurons (cell bodies lie in the brain and spinal cord) and postganglionic neurons (cell bodies lie outside the CNS). Cholinergic neurons include all preganglionic autonomic, postganglionic parasympathetic, neuromuscular junction, and few postganglionic sympathetic (sweat gland, skeletal muscle, and blood vessel). Adrenergic neurons include postganglionic sympathetic neurons, adrenal medulla, and hypothalamus.
Activation of sympathetic nervous system (fright and flight reaction) results in dilated pupil, tachycardia, hypertension, constricts skin blood vessel, bronchial dilatation, inhibits salivary secretion, urinary sphincter contraction, and detrusor relaxation. In contrast, parasympathetic stimulation results in constricted pupil, bradycardia, bronchial constriction, and increased salivary secretion.
Hypothalamus
Hypothalamus (below the thalamus) consists of various nuclei that synthesize and secrete neurohormones through pituitary. It consists of suprachiasmatic nuclei (controls sleep–wake cycle and circadian rhythm), paraventricular nucleus (secrete releasing hormone for TSH and ACTH), preoptic nucleus [secrete gonadotropin-releasing hormone (GnRH)], 39arcuate nucleus (secrete releasing hormone for prolactin), and periventricular nucleus (secrete growth hormone).
Fibers from supraoptic nucleus (secrete oxytocin) and paraventricular nucleus (secrete vasopressin) connect with posterior pituitary and the hormones are released at the end of nerve terminal in posterior pituitary. Hypothalamus controls sleep, circadian rhythm, temperature regulation, thirst, and hunger. It also controls the autonomic nervous system.