Neurosciences – Dentowesome

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Sutures and fontanelles present on skull

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Theories of cranial maldevelopment in craniosynostosis

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Classification of craniosynostosis

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Etiology and clinical features

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Syndromes associated with craniosynostosis

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Nonsyndromic craniosynostosis

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Clinical examination of craniosynostosis

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Functional consequences of craniosynostosis

Sources – Shafer’s textbook of oral pathology , slideshare.com

Image source – Google images , researchgate.net

HEART RHYTHMS – DR NATASHA UNANI

source – Nancy 13th edition

• The neural crest cells develop into numerous and varied cell types and migrate to regions far anterior (ventral) from their site of origin

• Peripheral nervous system (PNS) cells: glial cells & Schwann cells.
• Meninges: Specifically, the inner layers: the pia and arachnoid
• Melanocytes
• The Enteric Nervous System

• Pharyngeal Arch Components
  • Musculoskeletal structures
  • Pharyngeal arch cranial nerves

• Dorsal root ganglia
• Sympathetic chain ganglia
• Adrenal medullary cells
• Prevertebral ganglia

• Prosencephalon
• Mesencephalon
• Rhombencephalon
• Caudal neural tube

• Neural crest cells originate along the midline of the dorsal aspect of the neural tube.
• Somites lie lateral to them.

• The placodes are areas of thickened surface ectoderm that play an integral role in development of key cranial nerves (CNs 1, 2, and 8 – the solely sensory set) and also contribute to the development of merge the pharyngeal arch cranial nerves along with the neural crest cells.
• Examples of placodes:
  • The olfactory placode forms the olfactory nerves and epithelium.
  • The lens placode forms the optic nerve.
  • The geniculate placode contributes to the development of cranial nerve 7 (along with the neural crest cells of the 2nd pharyngeal arch).
  • The otic placode forms the vestibulocochlear nerve.

• Folding of the neural plate into the neural tube is key to the development of the neural crest cells.

• The neural folds form the neural crests.
• The neural groove forms the base of the neural tube.

• From top to bottom, the trilaminar germ disc comprises ectoderm, intraembryonic mesoderm, and endoderm.
• Mesoderm comprises somites and notochord (which induces the overlying ectoderm to form the neural plate).
  Then, draw the underlying endoderm.
• Along the floor of the ectoderm lies the neural folds (again the neural crests are the neural fold tips).
• The neural groove is the floor of the neural tube.

• The neural folds abut centrally, first, and remain open at their ends anteriorly and posteriorly.
• The neural crest lies along the dorsal neural tube.
  • Elsewhere we see that this is the roof plate of the neural tube and is biologically influenced by the neural crest cells.

• The neural tube is folded a long distance along its center but remains open at the anterior (cranial) and posterior (caudal) neuropores.
• The somites are visible, centrally, where the neural folds abut.
• The somites generate bumps that appear on the surface of the overlying neural tube.
• The neural crest cells make their migrations ventrally.

• Migrate to form the peripheral nervous system derivatives

• Ectoderm
• Mesoderm
• Neural tube
• Notochord
• Dorsal aorta
• A portion of the Gut Tube
• Somites (the paraxial mesoderm), which forms axial musculoskeletal elements, from lateral to medial:
  • Dermatome (dermis)
  • Myotome (muscle)
  • Sclerotome (skeleton): it migrates to form around the neural tube as the spine and posterior basal occipital bone.

• Portions of Cranial Nerves: 5, 7, 9, and 10 (the Pharyngeal Arch cranial nerves) and portions of CNs 3 and 8, as well.
• Dorsal root ganglia
• Sympathetic chain ganglia
• Adrenal medulla (the chromaffin cells)
• Prevertebral ganglia
• Enteric nervous system

• Don’t forget, however, that the neural crest cells are responsible for much more than the aforementioned peripheral nervous system derivatives.

• Additional peripheral nervous system cellular structures:, for instance – glial cells and Schwann cells.
• Melanocytes
• [Inner meningeal layers (pia and arachnoid – the leptomeninges)
• Musculoskeletal elements of the head and neck, such as the key cartilages and ear bones (learned elsewhere).

• The bending of light when a wave travels from a medium with one refractive index to a medium with another.

• Occurs within the photoreceptors of the retina, of which there are two main categories: cones and rods.
  • Cones detect color vision and require bright light.
  • Rods detect black/white (“night”) vision, so they only require low levels of illumination.

• The cornea has a pronounced curvature and is transparent to allow for the passage of light.
• Where the cornea ends, the outer layer becomes the sclera, which is opaque, so it blocks the transmission of light. The portion of the sclera we can see is the “white of the eye”; conjunctiva covers it.
• The biconvex lens is also transparent and serves to focus a target on the retina, specifically on the area of maximal visual acuity: the fovea centralis of the macula.
• The anterior cavity, which lies in front of the lens, contains aqueous humor.
• The posterior cavity, which lies behind the lens, contains vitreous humor – it’s referred to as the vitreous chamber, or vitreous body.
  • Like aqueous humor, vitreous humor is primarily water, but the presence of glycosaminoglycans and collagen gives it a gel-like composition, which helps maintain the eye’s shape.

There are 4 key anatomical components to optic refraction:

• Primary mediator is:
  • The Cornea
    It comprises 70% of the power of optic refraction through its pronounced curvature and through its corneal refractive index, which is substantially higher than that of the environmental air. The refractive index is the degree to which a medium bends light.
• Secondary mediators are:
  • Aqueous humor
  • The Lens
  • Vitreous humor

• Rays of light enter the cornea and bend to ultimately converge at the macula.

LIGHT DETECTION WITHIN THE EYE

Anatomy

• The uvea.
  • In front of the lens, lies the pigmented iris, which forms an adjustable diaphragm to funnel light through the pupil – the pigmented epithelium of the iris blocks light transmission and funnels light through the pupil.
  • Posterior to the iris, lies the ciliary body.
  • The choroid, which is a thin, brown, highly vascular layer is sandwiched between the sclera and retina; it nourishes the retina and removes heat produced during phototransduction, which is the process wherein the photoreceptors transform light into neural signal, and its brown pigment helps absorb light.
  • The ciliary body anchors suspensory ligaments, collectively called zonule, which stretch the lens and alter its refractive power.
• The retina lies internal to the choroid.
  • It transitions into optic nerve when it exits the eye, posteriorly, at the lamina cribrosa.
  • Key aspects of the retina are: the optic nerve head and the macula, the area of highest visual acuity (in the center of it, lies the fovea centralis).

• Rays of light enter the cornea and bend to ultimately converge at the macula.
• Electrical impulse, then, passes along the retina to the optic nerve.

• Emmetropia refers to normal refraction.
• Ametropia refers to abnormal refraction.
• In myopia, objects focus in front of the retina (the eyeball is too long).
• In hyperopia, objects focus behind the retina (the eyeball is too short).
• In astigmatism, there is image blurring irrespective of object distance from unequal curvatures in the various parts of the cornea.

Light reception occurs via photoreceptors within the retina.

• The pigmented layer is involved in photoreceptor metabolism; it comprises retinal pigemented epithelium (commonly abbreviated RPE), which captures light not picked up by the photoreceptors.
• The photoreceptor cells divide into cones and rods.
• Cones provide high-resolution color vision via photoreceptors that are large, conical, active in bright light, and are located predominantly centrally within the retina, meaning in the fovea of the macula,
• Rods provide low-resolution black/white (or “night”) vision via photoreceptors that are small, narrow and cylindrical, and require only dim light (low-level illumination), and are predominantly located peripherally within the retina – meaning outside of the macula.
• Differences in the number of receptor subtypes and their opsins – the photoreceptor proteins the determine the color waves they capture.
  • For the cones, there are generally three types of the photoreceptors which contain opsins that ultimately handle either red, green, or blue light.
  • Rods possess one type of photoreceptor, which contains rhodopsin.
  • The photoreceptor cell segments, themselves, are metabolically dependent upon the pigmented epithelium for photoreceptor regeneration and waste disposal.
• Interneuronal cell bodies comprise multiple cell body types and perform multiple functions, including passing forward electrical signal from the photoreceptor cells to the ganglion cells.
• The ganglion cells send axons, which form the nerve fibers, which are unmyelinated so as to NOT impeded the light from passing through the retina to the photoreceptor cell layer.

Summary

• Light passes through the retina and is captured by the photoreceptor cell segments where the phototransduction cascade occurs, which converts light to neural signal.
• Electrical signal is passed back through the retina.

• The anatomic location of the sleep center
• The physiology of the thalamocortical circuits
• The pathway for the generation of REM sleep.

• Baron Constantin von Economo first hypothesized about the anatomy of the sleep induction center when in 1916–17 he studied the clinical–pathologic correlations of patients who had died from encephalitis lethargica (aka von Economo’s encephalitis).
• The parkinsonian and oculomotor manifestations found in patients with that disorder led him to postulate that:
  • The sleep induction center lies within the anterior hypothalamus
  • The area for wakefulness lies, roughly, within the posterior hypothalamus/upper brainstem

• The area for non-REM sleep induction lies within the anterior hypothalamus, specifically in the ventrolateral preoptic area and the median preoptic nucleus.

Thalamocortical network

• Thalamocortical network generation of sleep electroencephalographic (EEG) patterns — sleep spindles and slow-wave sleep.

Major cell populations

• GABAergic reticular thalamic neurons (thalamus)
• T-type calcium channel thalamocortical neurons (thalamus)
• Cortical pyramidal cells (cerebral cortex)

Physiology

• The reticular thalamic nuclei gate the flow of information between the thalamus and cerebral cortex, and the thalamocortical neurons drive cortical EEG patterns through, at least in part, the low-threshold spike.
• The reticular thalamic nuclei causes GABAergic inhibition of thalamocortical cells.
• Eventually the thalamocortical membrane hyperpolarizes more negatively than –65 mV, which causes the T-type calcium channels to open, which generates a low-threshold spike: a burst of action potentials.
• The thalamocortical burst acts both on the reticular thalamic cells to facilitate their rhythmic oscillation and also on the cortical pyramidal neurons, which generate the EEG patterns observed during sleep.
• After the low-threshold spike, there is a refractory period for the thalamocortical neurons.
• As a byproduct of the refractory period, there is cessation of the excitatory thalamocortical inputs to such relay neurons as the lateral geniculate nucleus, which results in the phenomenon of sensory gating: the process wherein sensory stimuli that might otherwise wake us from sleep fail to reach our cerebral cortex.

REM SLEEP

• The putative primary REM-promoting region lies within the pons, in what is called the sublaterodorsal nucleus in the rat and the perilocus coeruleus in the cat.
  • This region excites the cortex to produce the characteristic EEG pattern of REM sleep.
  • And also excites a constellation of nuclei called the supra-olivary medulla to produce muscle atonia during REM sleep.

• REM inhibition comes from the midbrain (during wakefulness and non-REM sleep) from the ventrolateral periaqueductal gray area and the dorsal deep mesencephalic reticular nucleus, which tonically inhibit the sublaterodorsal nucleus/peri-locus coeruleus.

• REM disinhibition comes from the hypothalamus, from lateral hypothalamic melanin concentrating hormone nuclei, and from the medulla, from the dorsal paragigantocellular nucleus, which suppress the REM inhibition subnuclei and frees the REM promoting region to act on the supra-olivary medulla and cerebral cortex to produce REM sleep as previously described.

• The suprachiasmatic nucleus (the master timekeeper) to adjust the production and release of melatonin and, in turn, the timing of our internal clock with help from the retinohypothalamic pathway.
• Orexin (aka hypocretin), which acts via the flip-flop switch, and is notably dysregulated in narcolepsy.
• Wake-promoting cells that are: cholinergic, histaminergic, dopaminergic, serotinergic, noradrenergic.

• The suprachiasmatic nucleus lies just above the optic chiasm in the anterior hypothalamus and the paraventricular nucleus lies above it.

• During the DARK phase, descending hypothalamospinal projections from the paraventricular nucleus excite the cervical spinal cord.
• The cervical spinal cord, in turn, excites the superior cervical ganglion.
• The superior cervical ganglion activates the production of melatonin from within the pineal body, causing its release into circulation, which helps promote sleep.

• During the LIGHT phase, light passes along the retinohypothalamic pathway to excite the suprachiasmatic nucleus.
• The suprachiasmatic nucleus inhibits the paraventricular nucleus, which causes inhibition of the production and release of melatonin, thus promoting wakefulness.

• In the 1940s and 1950s neurophysiologists Giuseppe Moruzzi and H. W. Magoun performed a series of EEG studies to prove the existence of the wakefulness center.
• They described an active arousal generator in the brainstem reticular formation, coined the ascending reticular activating system, which was shown to directly and indirectly activate the cerebral cortex by way of diff use projection fibers; we addressed these intralaminar thalamic projections in the thalamus section.

• The cholinergic basal forebrain nuclei in the ventral surface of the frontal lobe (orbitofrontal gyri).
• The tuberomammillary nucleus in the center of the hypothalamus: it is the sole source of histamine in the brain.
• The substantia nigra and ventral tegmental area (which are dopaminergic): in the anterior midbrain.
• The laterodorsal tegmental and pedunculopontine nuclei in the lower midbrain and upper pons (which are cholinergic).
• The locus coeruleus (which is noradrenergic): in the posterior pons – (the largest concentration of locus coeruleus neurons lies within the pons).
• The dorsal group of raphe nuclei and (serotinergic) – in the central upper pons and midbrain.

• Amphetamines are adrenergic reuptake inhibitors and are stimulatory
  • They increase the amount of circulating monoamines.
• Serotonin-norepinephrine reuptake inhibitors (as their name states) increase serotonin and norepinephrine, which are wake-promoting.
• Cholinesterase inhibitors (like donepezil) are mentally energizing and used to help memory.

• Tricyclic antidepressants can be especially sedating because they often have both anti-cholinergic and anti-histaminergic properties.
• Diphenhydramine (Benadryl) is an anti-histamine, so it causes drowsiness and is used in over-the-counter sleep aids.

• Wake-promoting cells inhibit the sleep center and that the orexigenic cells excite the wake-promoting cells: they stabilize the biphasic aspect of this physiology.

• The sleep center inhibits the wake-promoting cells and the orexin area.

• An electrical engineering term for a switch that avoids transitional states; the circuit is in either one of two states but not a blend of both.
• If you are tired when you lie down, you quickly fall asleep, and when you’re ready to rise, you suddenly wake up.
• This is unlike most other key physiologic processes, which function along a continuum (eg, heart rate or respiratory rate).

• For reference, the SLEEP CENTER is the following important hypothalamic areas: the ventrolateral preoptic area and the median preoptic nucleus.

• OREXIN AREA is the region in the perifornical-lateral hypothalamic populated with orexigenic cells, which form the wakefulness stabilizer.

• Wake-promoting cells are those we addressed in our section on wakefulness neurobiology.

DR NATASHA UNANI

source – Nancy 13th edition

• Caudate
• Putamen
• Globus pallidus

• External (lateral)
• Internal (medial) segments.

• Descriptor for the globus pallidus because bundles of myelinated fibers traverse the globus pallidus, giving it a pale appearance.
• The pallidum is sometimes referred to as the paleostriatum because the globus pallidus is derived from the phylogenetically older portion of the brain — the diencephalon.
• The neostriatum refers to the caudate and putamen, which are derived from the phylogenetically newer part of the brain — the telencephalon.

• The corpus striatum also encompasses several fiber pathways that pass between the globus pallidus and the subthalamic nucleus and thalamus: the ansa lenticularis, lenticular fasciculus, subthalamic fasciculus, and thalamic fasciculus.These fibers comprise a considerable portion of the white matter region inferolateral to the thalamus, which is called the fields of Forel (aka prerubral fields or Forel’s Field H).

• Basal ganglia is more correctly referred to as the basal nuclei because a ganglion is a neuronal aggregation within the peripheral nervous system and the basal nuclei lie within the central nervous system, but the term basal ganglia is the common parlance, so we use it here.

• Caudate head in the wall of the frontal horn
• Caudate tail at the posterolateral tip of the thalamus (the body is not visible in this section)
• Lens-shaped lentiform nucleus, which subdivides into the putamen, laterally, and the globus pallidus, medially

• Thus, we can envision the lentiform nucleus as a globus pallidus core surrounded by a putaminal shell.
• The internal capsule lies in between the lentiform nucleus and the head of the caudate and thalamus.
• The external capsule lies in between the putamen and the claustrum.
• The extreme capsule lies in between the claustrum and the insula.

• The combined putamen and head of the caudate.
• The nucleus accumbens, which is the bridge that persists between the head of the caudate and putamen after the anterior limb of the internal capsule separates the head of the caudate from the putamen.
  • It is important in rewarding behavior.

• Optic tract
• Frontal horn of lateral ventricle
• 3rd ventricle
• Corpus callosum

• Caudate Head in the wall of the frontal horn
• Putamen
• Globus pallidus
• The lateral medullary lamina separates the putamen and globus pallidus.
• The medial medullary lamina subdivides the globus pallidus into an internal (or medial) segment and an external (or lateral) segment.
• The internal capsule lies in between the lentiform nucleus and the caudate.
• Beneath the globus pallidus, lies the basal forebrain and the horizontally-oriented anterior commissure in between them.
  • Note that the globus pallidus actually extends beneath the anterior commissure as the ventral pallidum

• corpus callosum
• & the subjacent lateral ventricular system:
  • frontal horn
  • atrium
  • temporal horn

• Caudate: head and body (the tail is not visible in this section)
• Putamen (anteriorly)
• Thalamus (posteriorly)

• Basal Ganglia Ischemic Stroke
• Basal Ganglia Hemorrhage

• The prefrontal cortex acts through innervation of the head and body of the caudate nucleus.
• The parietal lobes act through innervation of both the putamen and caudate.
• The primary auditory cortex projects to the caudoventral putamen and tail of the caudate.
• The visual cortices project primarily to the nearest portion of the caudate nucleus.

• The cerebellothalamic fibers from the corticopontocerebellar pathway, the medial lemniscus, the nigrothalamic fibers, and the spinothalamic fibers of the anterolateral system pathway.

• The term is sometimes broadened to include the cerebellothalamic fibers and it is also sometimes used synonymously with the term Field H1, just as the term lenticular fasciculus is sometimes used synonymously with term Field H2.
• The thalamic fasciculus projects to multiple thalamic nuclei, including the ventroanterior nucleus, which most notably communicates with the globus pallidus; the ventrolateral nucleus, which most notably communicates with the cerebellum; the dorsomedial nucleus, which most notably communicates with the prefrontal cortex and basal ganglia; and the centromedian and parafascicular nuclei (the main intralaminar nuclei), which most notably
  communicate with the striatum and frontal lobes.

• The striatum further subdivides into dorsal and ventral divisions.
• The dorsal striatum comprises the bulk of the caudate and putamen, whereas the ventral striatum is limited to only the ventromedial caudate and putamen, but the ventral striatum also encompasses the nucleus accumbens and select basal forebrain structures.
• The dorsal striatum is involved in a wide array of processes, including the sensorimotor circuits, whereas the ventral striatum associates principally with the limbic system and is primarily involved in emotional and behavioral processes.
• Just as the striatum divides dorsally and ventrally, so the pallidum further subdivides into a dorsal pallidum and ventral pallidum. Similar to the striatum, the dorsal pallidum refers to the bulk of the globus pallidus, whereas the ventral pallidum refers to the anteromedial portion of the globus pallidus that lies below the anterior commissure. However, although we consider the ventral striatum and ventral pallidum to be divisions of the striatum and pallidum, here, certain texts distinguish these ventral structures as entirely separate nuclei (ie, they distinguish the ventral pallidum from the pallidum, itself).
• The corpus striatum also encompasses several fiber pathways that pass between the globus pallidus and the subthalamic nucleus and thalamus: the ansa lenticularis, lenticular fasciculus, subthalamic fasciculus, and thalamic fasciculus. These fibers comprise a considerable portion of the white matter region inferolateral to the thalamus, which is called the fields of Forel (aka prerubral fields or Forel’s Field H).
• As a final note, the subthalamic nucleus and substantia nigra are functionally but not developmentally associated with the basal ganglia; therefore, although they are variably included as part of the basal ganglia, we do not include them in our definition of the basal ganglia, here, in accordance with the Terminologia Anatomica.

• The anterior cerebellar lobe
• The posterior cerebellar lobe

• The flocculonodular lobe: nodule in midline and flocculus out laterally.

• The midline cerebellum is the vermis (which means wormlike)
• Lateral to it, lies the paravermis (aka the intermediate zone)
• Lateral to it, lies the hemisphere (aka the lateral zone)

• Phylogenetically the oldest portion of the cerebellum and is referred to as the archicerebellum.
• It is derived from the flocculonodular lobe and the anterior tip of the vermis (the lingula).
• The vestibulocerebellum receives its name because of its midline vestibulo- and olivocerebellar fibers, which project to the deep, medial-lying cerebellar fastigial nuclei.
• It is important for equilibrium and eye movements.

• Phylogenetically the next oldest and is referred to as the paleocerebellum.
• It is derived from the anterior lobe and the majority of the vermian and paravermian posterior lobe.
• The spinocerebellum receives its name from its major input fibers: the spinocerebellar tracts.
• It plays a major role in postural stability.

• Phylogenetically the newest portion of the cerebellum and is referred to as the neocerebellum.
• It is derived from the remainder of the posterior lobe.
• The pontocerebellum receives its name because it acts through the corticopontocerebellar pathway.
• It is geared towards fine motor movements, which are typically goal-oriented.

• Nystagmus occurs from toxicity to the vestibulocerebellum, truncal ataxia occurs from toxicity to the spinocerebellum, and incoordination occurs from toxicity to the pontocerebellum.

• The pathology is predominantly restricted to the anterior superior cerebellar vermis. Because of this restricted area of injury, truncal ataxia is sometimes the sole deficit.

• Unilateral cerebellar lesions affect the ipsilateral side of the body.
• The midline cerebellum plays a role in posture whereas the lateral cerebellum assists in fine motor, goal-oriented skills.
• For instance, to stand upright, you need the midline cerebellum, and to play the piano, you need the lateral cerebellar hemispheres.

• The somatotopic map of the cerebellum is in concert with its functional layout: the role of the spinocerebellar, anterior lobe is to provide postural stability, which requires the limbs and trunk, and the role of the neocerebellar, posterior lobe is to provide goal-oriented, fine motor movements, such as those of the fingers and mouth.

BrainstemCerebellumDiencephalonCorpus callosum

Cerebral lobes

MidbrainPons, anterior-lying: basis

Medulla oblongata: pyramidal tracts

Clinical correlation, see callosal dysgenesis

The oft-forgotten limbic lobe surrounds the corpus callosum and diencephalon.

Frontal lobe (anteriorly)Parietal lobe (behind it)Occipital lobe (posteriorly)

Temporal lobe (inferiorly)