CEREBELLUM

- The cerebellum is the largest structure in the posterior fossa.

- it is attached to the dorsal aspect of the pons and rostral medulla by three white matter peduncles (feet)
and forms the root of the fourth ventricle.
- The cerebellum consists of a midline vermis, named for its wormlike appearance, and two large cerebellar
hemisphere.
- there are numerous fissures, the deepest of which called the primary fissure, separating the cerebellum
into an anterior lobe and a posterior lobe.
- on the ventral inferior surface, the posterolateral fissure separates the posterior lobe from the
flocculonodular lobe, a region with important connections to the vesicibular nuclei.
- the two floculli are connected to the midline structure called the nodulus by thin pedicles
- The nodulus is the most inferior portion of the cerebellar vermis
-Another important landmark on the inferior surface consists of the cerebellar tonsils.
- on midsagittal section, the beautiful branching pattern of the central cerebellar white matter and cortical
gray matter can be appreciated to which the latin term “arbor vitae” meaning “tree of life” has been
applied
- Instead of gyri, the small ridges that run from medial to lateral on the surface of the cerebellum are called
folia meaning “leaves”
- Removing the cerebellum from the brainstem reveals the three cerebellar peduncles (superior, middle
and inferior) which from the walls of the fourth ventricle
- The superior cerebellar peduncle mainly carries output from the cerebellum, while the middle
cerebellar peduncle and inferior cerebellar peduncle mainly carry inputs

- the superior cerebellar peduncle decussates in the midbrain at the level of the inferior colliculi
- because of the striking conjuction of fibers in the decussation, another name for the superior cerebellar
peduncle is the branchium conjunctivum
- because of its massive connections to the pons, an alternative name for the middle cerebellar peduncle is
branchium pontis
- the alternatiive name for the inferior cerebellar peduncle is

A. Anatomic divisions
a) Anterior lobe: anterior to primary fissure, receives majority of input from spinocerebellar tract
b) Posterior lobe: between primary and dorsolateral fissures; receives majority of input from
neocortex
c) Flocculonodular lobe: receives input from vestibular nuclei
Table 15.1. functional regions of the cerebellum
Region Functions Motor pathways
Lateral hemisphere Motor planning for extremeties Lateral corticospinal
Intermediate hemisphere Distal limb coordination Lateral corticispinal tract,
eubrospinal tract
Vermis and flocculonodular lobe Balance and vestibulo-ocular
reflexes

-Cerebellar lesion can often be localized on the basis of just a few simple principles
-Ataxia is ipsilateral to the side of a cerebellar lesion
Midline lesion of the cerebellar vermis or flocculonodular lobes mainly cause unsteady gait (truncal
ataxia) and eye movement abnormalities, which are often accompanied by intense vertigo, nausea,
and vomiting.
- Lesions lateral to the cerebellar vermis mainly cause ataxis of the limbs (appendicular ataxia)

FUNCTIONAL SUBDIVISION
1. Vestibulocerebellum - archicerebellum
a) Function
i. Orienting eyes during movement
 ii. Coordination position of head and limbs in response to position and motion through
connections with medial and lateral vestibulospinal tracts
iii. Has a role in smooth pursuit
b) Cerebellar component: flocculonodular lobe
c) Afferents: information from vestibular nuclei (mossy fibers) enters via inferior cerebellar peduncle
to synapse in the flocculonodular lobe.
d) Efferents : information from flocculonodular lobe returns to vestibular nuclei; this includes
inhibitory purkinje cell input to medial and lateral vestibular nuclei
e) Vestibular nuclei project to contralateral abducens nucleus and their axons also from the origins of
vestibulospinal tracts
f) NOTE: some outputs from the nodulus is transmitted to fastigal nucleus: from here, fastigal
nucleus axons influence vestibular nuclei (billaterally), the reticular formation, and contralateral
ventrolateral thalamus
g) Dysfunction: vertigo, mystagmus, truncal ataxia, deficits in visual pursuit

2. Spinocerebellum-vermis
a) Function
i. Monitors ongoing execution of movement (especially proximal limbs and axial musculature )
ii. Role in maintenance of muscle tone
b) Cerebellar components; vermis
c) Afferents (mossy fiber); primary somatosensory input via inferior cerebellar peduncle (from dorsal
spinocebellar and cuneocerebellar tract, mostly muscle spindle input) and superior cerebellar peduncle (from
ventral and rostal spinocerebellar tracts)
d) Efferents: information from vermis projects to fastigial nucleus.
e) Efferents from fastigial nucleus
i. Descending fibers to ipsilateral and contralateral reticular formation, origin of reticulospinal
tracts
ii. Descending fibers to ipsilateral and contralteral vesticular nuclei, origin of vestibulospinal
tracts
iii. Ascending fibers via superior cerebellar peduncle to primary motor cortex through synaptic
relay in ventrolateral thalamic and red nuclei, influencing descending motor pathways
f) Dysfunction: syndromes may overlap with paravermal syndormes, truncal ataxia
3. Spinocerebellum-paravermis (intermediate lobe)
a) Function
i. Monitors ongoing execution of limb movement
ii. Postural tone
iii. Modulates descending motor systems
b) Cerebellar component: paravermal region and anterior lobe
c) Afferents to paravermis: somatosensory information from dorsal spinocerebellar and
cuneocerebellar tracts (via inferior cerebellar peduncle) ventral and rostal spinocerebellar tract (via superior
cerebellar peduncle)
d) Efferents: information from anterioir lobe projects to nucleus interpositus (globose and emboliform
nuclei)
e) Efferents from nucleus interpositus (ascends via decussating superior cerebellar peduncle ) to
i. Contralateral red nucleus (its axon descend in rubrospinal tract, which decussates immediately
after it originates)
ii. Contralateral ventrolateral thalamic nucleus, which projects to cerebral cortex
f) Dysfunction: limb dysmetria
4. Cerebrocerebellum - neocerebellum
a) Function: initiation and timing of movement; precision in control of rapid movements and
conscious assessment of errors in movement (fine dexterity)
b) Cerebellar component: lateral cerebellar hemispheres (posterior lobes)
c) Afferents (mossy fiber); corticopontocerebellar fibers via middle cerebellar peduncle
d) Efferents from dentate nucleus (ascends via decussating superior cerebellar peduncle) to
i. Contralateral red nucleus (dentatorubral tract)
ii. Contralateral ventrolateral thalamic nucleus (dentothalamic tract), which projects to cerebral
cortex
CEREBELLAR NUCLEI
- All outputs from the cerebellum are relayed by these nuclei
- receive collateral fibers of cerebellar inputs on their way to the cerebellar cortex
- the deep cerebellar nuclei or roof nuclei are from lateral to medial, the dentate nucleus, emboliform
nucleus, globose nucleus, and fastigal nucleus
- a mnemonic is “ don’t eat greasy foods” (dentate, emboliform, globose, fastigial)

-The dentate nuclei are the largest of the deep cerebellar nuclei, and they receive projections from the
lateral cerebellar hemispheres
- the fastigal nuclei receive input from the vermis and a small input from the flocculonodular lobe
- most fibers leaving the inferioir vermis and flocculi project to the vestibular nuclei, which though located
in the brainstem rather than the cerebellum, function in some ways like additional deep cerebellar nuclei.
Table 15.2 main cerebellar output pathways
Region Deep nuclei Cerebellar peduncle Main output targets or equivalent
 Lateral Hemispheres Dendate nucleus Superior cerebellar peduncle Ventrolateral nucleus of thalamus
(VL), parvocellular red nucleus
 Intermediate Interposed nuclei Superior cerebellar peduncle VL, magnocellular red nucleus
Hemispheres

 Vermis Pastigal nuclei Superior cerebellar peduncle VL, tectum

Uncinate fasciculus,
juxtarestiform body
 Vermis AND Vestibular nuclei juxtarestiform body Medial longitudinal fasciculus
Flocculonodular Lobe (eye movement pathways)

* the uncinate fasciculus travels with the superior cerebellar peduncle

* the juxtarestiform body travels with the inferior cerebellar peduncle

CYTOARCHITECTURE of CEREBELLAR CORTEX

1. Granular layer: contains mainly granule cells, which receive most input from the mossy fibers, and golgi
cells which modify granule cell output
2. Purkinje cell layer: contains purkinje cells, the major source of output of cerebellar cortex
3. Molecular layer: contains mainly axons from granule cells (forming parallel fibers). purkinje cell
dendrites, basket cells, stellate cells
VASCULAR SUPPLY
- blood supply to the cerebellum is provided by three branches of the vertebral and basilar arteries
1. The posterior inferior cerebellar artery (PICA)
2. The anterior inferior cerebellar artery (AICA)
3. The superior cerebellar artery (SCA)

MUST KNOW:
- irreversible brain damage (brain death) occurs of blood supply to the brain is interrupted for more than a
few minutes
- the internal carotoid arteries provide blood supply to the rostal parts of the brain, whereas the vertebral
arteries provide blood supply to the posterior parts of the brain
- the anterior cerebral artery and its branches provide blood supply to the medial surface of the
hemisphere as far back as the parietoccipital fissure
- the medial cerebral artery and its branches provide blood supply to most of the lateral surface of the
hemisphere.
- the posterioir cerebral artery, the terminal branch of the basilar artery supplies the medial surfaces of the
occipital, temporal, and the caudal part of the parietal lobes
- the circle of willis comprises the major site of intracranial collateral circulation
- Extrinsic factors that regulates cerebral circulation include systemic blood pressure, blood viscosity, and
vessel lumen.
- intrinsic factors that regulate cerebral circulation include autoregulation (the most effective) and
biochemical alterations in carbon dioxide, oxygen, and pH
- consciousness is lost if thr blood supply is interrupted for about 5 seconds
- it is estimated that about 15 percent of cardiac output reaches the brain; about 20 percent of oxygen
utilization of the body Is consumed by the adult brain and as much as 50 percent by the infant brain
- the blood flow through the human brain is estimated to be 800 ml/min, or approximately 50ml/100g of
brain tissue per minute
- blood flow increases with an increase in functional activity of the brain or region within it.
- the blood flow is markedly increased in the sensory motor area on vigorous exercise of the contralateral
limb
- cerebral blood flow is faster in gray matter ( 70 to 80 ml / 100g per minute) than white matter ( 30ml/
200 g per minute)
- irreversible brain damage will occur if the cerebral blood flow is less than 15 ml/ 100 g per minute

HIGH YIELD INTERNAL CAROTID ARTERY

A. The ophthalmic artery enters the orbit with the optic nerve (CN II). the central artery o the retina is a
branch of the ophthalmic artery. Occlusion results in blindness
B. The posterior communicating artery irrigates the hypothalamus and ventral thalamus
An aneurysm of this artery is the second most common aneurysm of the circle of wills. It commonly
results in third-nerve palsy
C. The anterior choroidal artery arises from the internal carotiod artery. It is not part of the circle of willis.
It perfses the lateral geniculate body, globus pallidus, and posterior limb of the internal capsule.
D. The anterioir cerebral artery supplies the medial surface of the hemisphere from the frontal to the
parietoccipital sulcus
a) The anterior cerebral artery irrigates the paracentral lobule, which contains the leg foot area the
motor and sensory cortices
b) The anterior communication artery connects the two anterioir cerebral arteries. It is most
common site of aneurysm of the cicle of wills, which may cause bitemporal lower
quadrantanopia.
c) The medial striate arteries are the penetrating arteries of the anterioir cerebral artery. They supply
the anterior portion of the putamen and caudate nucleus and the anteroinferior part of the
internal capsule.
E. The middle cerebral artery
a) This middle cerbral artery supplies the lateral convexity of the hemisphere, including
i. Broca’s and wernicke’s speech areas
ii. The face and arm areas of the motor and sensory cortices
 iii. The frontal eye field
2. The lateral striates arteries ( lenticulostriate) are the penetrating branches of the middle cerebral artery.
They are the arteries of stroke, and they supply the internal capsule, caudate nucleus, putamen, and globus
pallidus
- blood supply of internal capsule comes primarily from the lateral striate of the middle cerebral artery and
the anterior choroid artery.

HIGH YIELD VERTEBROBASILAR SYSTEM

A. The vertebral artery is branch of the subclavian artery.
- gives rise to the anterior spinal artery and the posterior inferioir cerebrllar artery (PICA),
which supplies the dorsolateral quadrant of the medulla.
- this quadrant includes the nucleus ambiguus ( CN IX,X, and XII) and the inferior surface of the cerebellum
B. The basilar artery is formed by two vertebral arteries
- it gives rise to the ff. Arteries:
1. The paramedian branches of the pontine arteries supply the base of the pons, which includes the
corticospinal fibers and the exiting root fibers of the abducens nerves (CN VII)
2. The labryinthine artery arises from the basilar artery in 15 % of people. It arises from the anterior
from the anterior inferior cerebellar artery in 85 % of people.
3. The anterior inferior cerebellar artery (AICA) supplies the caudal lateral pontine tegmentum,
including CN VII, the spinal trigmental tract of CN V, and the inferior surface of the cerebellum.
4. The superior cerebellar artery supplies
a) Dorsolateral tegmentum of the rostal pons (I.e., rostal to the motor nucleus of CN V)
b) The superior cerebellar peduncle
c) Superior cerebellar peduncle
d) Superioir surface of the cerebellum and cerebellar nuclei
e) Cochlear nuclei.
5. The posterior cerebral artery is connected o the carotid artery though the posterior communicating
artery.
a) Major blood supply to the midbrain
b) Thalamus
c) Lateral and medial geniculates bodies
d) Occipital lobe ( which includes the visual cortex and the inferior surface of the temporal lobe,
including the hippocampal formation)

- occlusion of this artery results in a contralateral hemianopia with macular sparing.

CIRCLE OF WILLIS
- proximal portions of the anterior, middle and posterior cerebral arteries connected by the anterior and
posterior communicating arteries from a circle, the circle of willis, around the infundibulum of the pituitary
and the optic chiasm.
- the circle constitutes an important anastomotic channel between the internal carotid and the vertebral
basilar systems
-when either the internal carotid arteries (anterioir circulation) or the vertebral basilar system (posterioir
circulation ) becomes occluded, collateral circulation in the circle of willis will provide blood to the area
deprived of blood supply
- the circle of wills is completed in only 20 percent of individuals.
- in the majority of individuals, variation in size and/or origin of vessels is the rule.

HISTOLOGY OF CEREBRAL VESSELS NICE to KNOW

- Cerebral arteries differ from arteries elsewhere in the body in the ff. Features.
-thinner walls
-absent external elastic laminae
-presence of astrocytic processes
-presence of a perivascular reticular sheath consisting of arachnoid trabeculae ( the latter acquire an
outer pial membrane when the vessel penetrates the brain substance)
-cerebral capillaries are structurally similar to capillaries elsewhere, except for being surrounded by
perivascular glial (astrocytic) processes
-cerebral veins have thinner walls and are devoid of valves and muscle fibers. The absence of valves allows
reversal of blood flow when occlusion of the human occurs in disease.

COLLATERAL CIRCULATION nice to know

- main purpose is to ensure a continuing blood flow to the brain in case a major occlusion of a feeding vessel

The following are the major sites of collateral circulation:

1. Extracranial anastomoses are found between cervical vessels, such as the vertebral and external carotids
of the same side.
2. Extracranial intracranial anastomoses occur between branches of the external carotid and the opthalmic
artery
3. Intracranial anastomoses occur in the circle of wills.

FACTORS REGULATING CEREBRAL CIRCULATION good to know

- cerebral blood flow is a function of the pressure gradient and cerebral vascular resistance
- the pressure gradient is determined primarily by arterial pressure
- resistance is a function of blood viscosity and size of cerebral vessels.

Extrinsic factors
1. Systemic blood pressure
2. Blood viscosity
a) Cerebral blood flow is inversely proportional to bllood viscosity in humans
b) A major factor controlling blood viscosity is the concentration of red blood cells
c) A reduction in blood viscosity , as occurs in anemia, will increase cerebral blood flow
d) An increase in viscosity, as occurs in polycythemia will decrease cerebral blood flow.
3. Vessel lumen
a) Minor reductions in the lumina of carotif and vertebral arteries are without effect on cerebral
circulation.
b) The vessel lumen must be reduced by 70 to 90 percent before a reduction in cerebral circulation
occurs.

INTRINSIC FACTORS
A. AUTOREGULATION
The single most important factor controlling cerebral circulation is the phenomenon of autoregulation, by
which smooth muscles in small cerebral arteries and arterioles can change their tension in response to
intramural pressure to maintain a constant flow despite alterations in perfusion pressure.
- cerebral blood vessels constrict in response to an increase in intraluminal pressure and dilate in response to
a reduction in intraluminal pressure.

INTRINSIC FACTORS
B. BIOCHEMICAL FACTORS
1. CARBON DIOXIDE.
- ARTERIAL PCO2 is a major factor in the regulation of cerebral blood flow
- hypercapnia (high pco2) produces marked vasodilatation and an increase in cerebral blood flow
- hypocapnia (low pco2) - vasoconstriction, decrease cerebral blood flow
- inhalation of carbon dioxide increases cerebral blood flow, whereas hyperventilation decreases cerebral
blood flow.
- under normal conditions, it is estimated that a change of 1 mmHg in PCO2 will induce a 6 percent change
in cerebral blood flow.
1. Biochemical factors
 - the ph of the cerebrospinal fluid (csf) reflects the arterial pco2 and is also influenced by the level of
bicarbonate in the CSF
- the effect of carbon dioxide on cerebral blood flow is important in dampening the effects of tissue PCO2 in
areas of brain ischemia
- the increase in cerebral blood flow in such areas helps to wash out metabolically produced carbon dioxide
and thus reestablishes hemeostasis of brain pH.
2. OXYGEN
- moderate changes in arterial po2 do not alter cerebral blood flow
- more marked changes in arterial po2 after cerebral blood flow in a manner that is the reverse of that
described for pco2
- low po2 (below 50 mmHg) will increase cerebral blood flow, and high PO2 will decrease cerebral blood
flow
3. pH
-cerebral blood flow increases with the towering of the pH and decreases in alkalosis

CEREBRAL VENOUS DRAINAGE

- cerebral venous drainage occurs through two systems, the superficial and the deep.

SUPERFICIAL VENOUS SYSTEM

1. SUPERIOR CEREBRAL GROUP
2. MIDDLE CEREBRAL GROUP
3. INFERIOR CEREBRAL GROUP

1. SUPERIOR CEREBRAL GROUP

- drainage the dorsolateral and dorsomedial surfaces of the hemisphere and enter the superior sagittal
sinus at a forward angle against the flow of blood
- most prominent of these veins in the central sulcus is called superior anastomotic vein of trolard, which
interconnects the superior and middle groups of veins.

2. MIDDLE CEREBRAL GROUP

- run along the sylvian fissure, drain the inferolateral surface of the hemisphere and open into the cavernous
sinus.

3. INFERIOR CEREBRAL GROUP

- these veins drain the inferior surface of the hemisphere and open into the cavernous and transverse sinuses
- the middle and inferior groups are connected by the inferior anastomic vein of Labbe, which crosses the
temporal lobe aboput 5 cm behind its tip
- the medial surface of the hemisphere is drained by anumber of veins that open into the superior and
inferior sagittal sinuses, as well as into the basal vein and the great cerebral vein of Galen.

DEEP VENOUS SYSTEM

- INTERNAL CEREBRAL VEIN
- Terminal vein (thalamostriate)
- septal vein
-BASAL VEIN OF ROSENTHAL
- drains blood from base of brain
-GREAT CEREBRAL VEIN OF GALEN
- empty into the straight sinus

DURAL VENOUS SINUSES

-cerebral dural venous sinuses are lined by endothelium and are devoid of valves
- lie between the periosteal and meningeal layers of the dura mater
Serve as low-pressure channels for venous blood flow back to the systemic circulation

-the superior sagittal sinus and the inferior sagittal sinus lie in the superior and inferior margins of the falx
cerebri , respectively.
- the superficial cerebral veins drain into the superior and inferior sagittal sinuses
- the superior sagittal sinus, in addition, drains cerebrospinal fluid from the subarachnoid space via
arachnoid matter (arachnoid villi ), into the superior sagittal sinus.

- the inferior sagittal sinus is joined by the great vein of galen to form the straight sinus (rectus sinus)
located at the junction of the falx cerebri and tentorium cerebelli
- the straight sinus drains into the confluence of sinuses
- the two transverse sinuses arise from the confluence of sinuses (torcular herophili) and pass laterally and
forward in a groove in the occipital bone.
- at the occipitopetrosal junction, they curve downward and backward as the sigmond sinuses, which drains
into the internal jugular vein.

LIMBIC SYSTEM
ROLE OF THE LIMBIC SYSTEM
-serve as link between cortical sensory association areas, the subcortical autonomic and endocrine centers
and the prefrontal association cortex.
- it mediates the effects of emotion on motor function

-limbic lobe
- parahippocampal gyrus
-cingulate gyrus
-subcallosal gryus
-amygdala
-Hippocampal formation
- hippocampus
-dentate gyrus
-supracallosal gyrus (indusium griseum)
-fornix
-septal area
-subiculum

HIPPOCAMPAL FORMATION
1. HIPPOCAMPUS
- hidden beneath the parahippocampal gyrus, rolled inwardly
2. DENTATE GYRUS
- lies on upper surface of parahippocampal gyrus, serve as input station for hippocampal formation
3. SUBICULUM
-transitional cortex from archicortex of hippocampal to 6 layered neocortex

1. HIPPOCAMPUS

-divided into 4 fields - cornus ammonis (CA)

- CA 1 field (sommer’s sector) is highly vulnerable to anoxia (temporal lobe epilepsy trigger zone)
- plays a role in declarative or associative memonry, attention and alertness, behavioral, endocrine and
visceral functions

2. AMYGDALA
- located deep to uncus near the tail of caudate and above the most rostal part of lateral ventricle inferior
horn
- responsible for learning and maintenance of link between a stimulus and its emotional value
- stimulation- fear and anxiety, deja vu
- lesion - e.g. kluver-bucy syndrome
- establish association between sensory inputs and various affective/emotional states
-activity of neurons within the amygdala is increased during states of apprehension, or frightening stimuli
- regulates endocrine activity, sexuall behavior, and food and water intake by modulating hypothalamic
activity.

AMYGDALOID COMPEX
1. INPUT
-from primitive temportal cortex and sensory and sensory association cortex, opposite amygdala (via
anterior commissure)
2. OUTPUT
- to hypothalamus (direct amygdalo-fugal pathway), septal area and hypothalamus (via striaterminalis)

BASAL GANGLIA
Topography:
-caudate nucleus
-putamen
-globus pallidus
-substantia nigra
-subthalamic nucleus

BASAL GANGLIA TERMINOLOGY

CORPUS STRIATUM
1. CAUDATE NUCLEUS
- a large c-shaped mass of gray matter closely related to the lateral ventricle and lies lateral to the thalamus
- divided into a head, a body, and a tail
2. LENTIFORM NUCLEUS
-a wedge-shaped mass of gray matter whose broad convex base is directed laterally and its blade medially
- related medially to the internal capsule thalamus
- related laterally to a thin sheet of white matter, the external capsule, separating it from a thin sheet of gray
matter, the claustrum
- a vertical plate of white matter divides the nucleus into the putamena nd the globus pallidus.

CLAUSTRUM
- a thin sheet of gray matter separated from the lateral surface of the lentiform nucleus by the external
capsule
- has reciprocal connection with all crtical areas including insular and visual cortex and limbic system
- function: regulation of emotion and sexual arousal

NUCLEUS ACCUMBENS

INTERNAL CAPSULE

BASAL GANGLIA LOOPS

DIRECT PATHWAY
- facilititates movement
- dopamine acts on D1 receptors

INDIRECT PATHWAY
-inhibits movement
-dopamine acts on D2 receptors

CONNECTIONS OF THE CORPUS STRIATUM AD GLOBUS PALLIDUS

-the caudate nucleus and the putamen form the main sites for receiving input from the cortex
- receive no direct input from or output to the spinal cord

PARKINSON’S DISEASE and RELATED DISORDERS

-parkinson’s diease is a common idiopathic neurodegenerative condition cause by loss of dopaminergic
neuron in the substantia nigra pars compacta.
- it is characterized by asymmetrical resting tremor, bradykinesia, rigidity, and postural instability,
which usually respond to therapy to levodopa
- parkinsonism and parkinsonian signs are more general terms used to describe several other conditions
that have some features of parkinson’s disease, especially the bradykinesia and rigidity.
 DIENCEPHALON
- sits on top the brain stem
- enclosed by the cerebral hemispheres
-made of three parts
1. Epithalamus
2. Thalamus
3. Hypothalamus

Epithalamus
-above the thalamus and forms the roof of the 3rd ventricle
- contains the pineal gland which releases melatonin (involved in sleep/wake cycle and mood)
- contains a structure called habenula - involved in food and water intake

THALAMUS
Group of nuclei that from the lateral boundary of the 3rd ventricle.

BOUNDARIES of the THALAMUS

Anterior: interventricular formane
Posterior: posterior commisure
Lateral : internal capsule
Superior: part of the floor of the lateral ventricle
THALAMIC FUNCTIONS
- process all sensory information (except olfactory)
-Regulates execution of motor programs
-Controls level of cortical excitability
-Influences motivational and emotional responses.
-functions as gate or filter: “switchboard”- what input is allowed through for
processing
- intergration of motor and sensory input to the cortex

TOPOGRAPHICAL SUBDIVISION of the THALAMUS

- subdivided by a fiber tract: internal lamina (Y-shaped) separates 6 groups:
1. Lateral: dorsal and ventral tier
2. Medial
3. Anterior
4. Intralaminar
5. Midline
6. Reticular
RELAY and ASSOCIATION NUCLEI
- anterior: anterior nucleus
-lateral
Ventral: VA,VL, VP(VPM, VPL)
Dorsal: pulvinar, LD, LP
-medial: dorsomedial nucleus
-lateral (visual) and medial (auditory) geniculate nucleus

DIFFUSION PROJECTION NUCLEI

-intralaminar: contromedian nucleus (ARAS input)
-reticular: lies like a mantle covering the lateral part of the thalamus, separated by the external medullary
lamina (not shown in schematic)
No projections to the cortex, only the thalamic nucleus with inhibitory output to toher
thalamic nuclei
- midline nuclei: dorsal half of the wall of the 3rd ventricle

Major Thalamic Nuclei

Nuclei Main inputs Main outputs Proposed functions
Ventral posterior lateral Medial lemniscus, Somatosensory cortex Relays somatosensory
nucleus (VPL) spinothalamic tract spinal inputs to cortex
Ventral posteromedial Trigeminal lemniscus, Somatosensory and taste Relays somatosensory
nucleus (VPM) trigeminothalamic tract, cortex cranial nerve inputs
taste inputs and taste cortex
Lateral geniculate Retina Primary visual cortex Relays visual inputs to
nucleus (LGN cortex
Medial geniculate Inferior colliculus Primary auditory cortex Relays auditory inputs
nucleus (MGN) to cortex
Ventral lateral nucleus Internal globus Motor, premotor, and Relays basal ganglia
(VL) pallidus, deep supplementary motor cortex and cerebellar inputs
cerebellar nuclei, to cortex
substantia nigra pars
reticulata
Ventral anterior Substantia nigra pars Widespread to frontal lobe, Relays basal ganglia
nucleus (VA) reticulata, internal including prefrontal, and cerebellar inputs
globus pallidus, deep premotor, motor, and to cortex
cerebellar nuclei supplementary motor cortex
Pulvinar Tectum Parietotemporo- occipital Behavior orientation
(extrageniculate visual association toward relevant visual
pathway), other sensory and other stimuli
inputs
Lateral dorsal nucleus See anterior nucleus Functions with nuclei
Ventral medial nucleus Midbrain reticular Widespread to cortex May help maintain
formation alert, conscious state
Mediodorsal nucleus Amygdala, olfactory Frontal cortex Limbic pathways,
(MD) cortex, limbic basal major relay to frontal
ganglia cortex
Anterior nucleus Mammillary body, Cingulate gyrus Limbic pathways
hippocampal formation
Midline thalamic nuclei Hypothalamus, basal Amygdala, hippocampus, Limbic pathways
Para ventricular, forebrain, amygdala, limbic cortex
parataenial, hippocampus
intermediodorsal,
rhomboid, reuniens
(medial ventral)
Rostral intralaminarDeep cerebellar nuclei, Cerebral cortex striatum Maintain alert
nuclei Central medial globus pallidus, consciousness; motor
nucleus Paracentralbrainstem ascending relay for basal ganglia
nucleus Central lateral reticular activating and cerebellum
nucleus systems (ARAS),
sensory pathways
Caudal intralaminar Globus pallidus, Striatum, cerebral cortex Motor relay for basal
nuclei Centromedian ARAS, sensory ganglia
nucleus Parafascicular pathways
nucleus
Reticular nucleus Cerebral cortex, Thalamic relay and Regulates state of
thalamic relay and intralaminar nuclei, ARAS other thalamic nuclei
intralaminar nuclei,
ARAS

HYPOTHALAMUS
- the hypothalamus consists primarily of gray matter formed into matrix of nuclei located in the middle of
the base of the brain and encapsulates the ventral portion of the tthird ventricle.
HYPOTHALAMIC ANATOMY
- It is located below the thalamus on each side of the third ventricle and is continuous across its floor
Boundaries:
- anterior - optic chiasm and anterior commissure
- posterior - mammillary bodies
- superior - hypothalamic sulci
- inferior - hypohysis

HYPOTHALAMIC REGION
- divided rostrocaudally into 4 regions:
1. Preoptic region (most rostal)
2. Anterior region
3. Tuberal region
4. Posterior region (most caudal)

Anterior Middle/tuberal Posterior

Preoptic Lateral Mamillary
Supraoptic Arcuate Posterior
Suprachiasmatic Dorsomedial
Paraventricular Ventromedial
Anterior
 Hypothalamic Region and function
Region Nuclei Function
Preoptic Heat dissipation sleep
Supraoptic Water balance (ADH secretion)
Suprachiasmatic Biological clock
Anterior Paraventricular Water balance (ADH secretion) satiety
Anterior Parasympathetic Heat dissipation
Middle Lateral Hunger Cortical arousal
Arcuate Secretion of peptide releasing hormone
Dorsomedial GI tract
Ventromedial Satiety
Posterior Posterior Heat conservation Sympathetic Cortical arousal
mamillary Feeding

HYPOTHALAMIC ZONE SLEEP AND SLEEP-WAKE CYCLE

- it can be divided into 3 parasagittal zones via the - SUPRACHIASMATIC NUCLEUS - biological
fornix, a bundles of fiber tracts that connect the clock- circardian rhythm
hippocampus to the mamillary bodies: - PRE-OPTIC area - induced sleep
1. Periventricular - lateral and posterior hypothalamus - cortical
a) Dorsal longitudinal fasciculus arousal
2. Medial hypothalamic
a) Anterior or supraoptic
b) Middle or tuberal
c) Posterior or mamillary
3. Lateral hypothalamic
a) Lateral nucleus
 HYPOTHALAMUS: INTEGRATIVE FUNCTIONS
- the hypothalamus helps regulate five basic physiological needs:
1. Controls BP and electrolyte (drinking and salt appetite)
2. Regulates body temperature through influence both of the ANS and of brain circuits directing motivated
behavior (e.g. behavior that seeks a warmer or cooler environment).
3. Regulates energy metabolism through influence on feeding, digestion and metabolic rate.
4. Regulates reproduction though hormonal control of mating, pregnacy and lactation
5. Direct responses to stress by influencing blood flow to specific tissues and by stimulating the secretion of
adrenal stress hormones.
1. Temperature regulation
a) Anterior- parasympathetic- vas
4. Emotion- numerous interconnection with the limbic system and cerebral cortex
a) Ventromedial nucleus- rage responses
5. Sleep-wakefulness regulation
a) Dorsolateral mamillary region - somnolence via ARAS
b) Suprachiasmatic nucleus - circadian rhythm
6. Endocrine function
a) Arcuate nucleus and parts of periventriular zone secretes Releasing hormones ( TRH, GHRH, CRH,
GnRH, PRH)
INTRACELLUMAR AND EXTRACELLUMAR ION CONCENTRATIONS

ION extracellular intracellular equilibrium

(mM) (mM) potential
(mV)
Na+ 140 15 +60
K+ 3.5 120 -95
Ca2+ 2.5 0.0001 +136
(unbound
ca2+)
Cl- 120 5 -86
EQUILIBRIUM POTENTIAL - THE NERNST EQUATION
- the differential ion concentrations on the inside versus the outside of the cell are maintained by the function
of the cell membrane.
- the movement of ions until they reach a steady state. Ions move along a concentration gradient.
- uncharged particles will move across the membrane until the same concentration is achieved on both sides
(diffusion), because ions are charged, their movement causes an electrical gradient.
- charged ions rapel ions with the same charge at the membrane along the concentration gradient, there is a
build-up of charge preventing more ions from moving across the membrane.

- for example, the K+ concentration inside (I) the cell (120 mM) is higher than outside (o) the cell (3.5 mM).
K+ will move along the concentration gradient across the membrane to the outside of the cell an take the
positive charge with it.
- the potential of the inside of the cell is negative because it is constantly losing K+ to the outside of the cell
- the net flow is that the inside of the cell is losing ions.
- as these K+ ions move, they generate a potential gradient , or electrical gradient, across the membrane.
- at some point, this electrical gradient will prevent the further movement of K+ as positive charge build-up
on the other side of the membrane will repel positive charges from crossing over.
 EQUILIBRIUM POTENTIAL
- equilibrium potential (also called electrochemical equilibrium) is thus achieved.
- this equilibrium potential can be expressed by the nernst equation
- the nernst equation takes several physical constants and the ion gradient or ion concentration inside the cell
and outside the cell, to determine the potential at which there will be no more net movement of ions.
- the equilibrium potential for K+ is at -95mV

Neurotransmitters in the CNS

Neurotransmitter Postsynaptic effect
Acetylcholine (ACh) Excitatory
Glutamine Excitatory
Amino acids Aminobutyric acid (GABA) Inhibitory
Glycine Inhibitory
Excitatory (via D1 receptors)
Dopamine Inhibitory (via D2 receptors)
Norepinephrine Excitatory
 Epinephrine Excitatory
Biogenic Serotonin Excitatory or Inhibitory
amines Histamine Excitatory
Purines Adenosine triphosphate (ATP) Excitatory/ neuromodulatory
Substance P Excitatory
Neuropeptide Metenkephalin Inhibitory
s Opioids Inhibitory
Adrenocorticotropin Excitatory

SPINAL CORD
- runs through the vetrebral canal
-extends from foramen magnum to second lumbar vertebra
- regions
-cervical
-thoracic
-LUMBAR
-SACRAL
- COCCYGEAL
CORD SEGMENTS VERTEBRAL SPINES
- gives rise to 31 pairs of spinal nerves
C-1 C-1
-cervical and lumbosacral enlargement
- conus medullaries- tapered inferior end C-7 C-6
- ends between L1 and L2 T-6 T-4
- cauda equina - origin of spinal nerves extending L-1 T-10
inferiorly S-1 T-12 to L-1
from conus medullaries.

SPINAL CORD AND VERTEBRAL SPINES

 MENINGES
connective tissue membranes
 dura mater- outermost layer; continuous with epineurium of the spinal nerves
 arachnoid mater- thin and wispy
 Pia mater boundly tightly to surface
 Forms the filum terminale
 anchors spinal cord to coccyx
 Forms the dendiculate ligaments that attach the spinal cord to the dura
 SPACES
 epidural- external to the dura
 anesthestics injected here
 fat-fill
 subdural space- serous fluid
 subarachnoid- between pia and arachnoid
 filled with CSF

CROSS SECTION OF SPINAL CORD

- anterior median fissure and posterior median sulcus

-deep clefts partially separating left and right
halves
-gray matter; neuron cell bodies, dendrites, axons
-divides into horns
-posterior (dorsal) horn
-anterior (ventral) horn
-lateral horn
- white matter
-myelinated zxons
-divided into three columns (funiculi)
-ventral
-dorsal
-lateral
- each of these divided into sensory or motor tracts

ORGANIZATION OF SPINAL CORD GRAY MATTER

- recall, it is divided into horns
-dorsal, lateral (only in thoracic region), and ventral
- dorsal half - sensory roots and ganglia
- ventral half- motor roots
- based on the type of neurons/ cell bodies located in each horn, it is specialized further into 4 regions
-somatic sensory (SS) - axons of somatic sensory neurons
- visceral sensory (VS)- neurons of visceral sensory neurons
-visceral motor (VM) - cell bodies of visceral motor neurons
Somatic motor (SM) - celll bodies of somatic motor neurons
Rexed terminology Older terminology
Lamina I Posteromarginal nucleus
Lamina ii Substantia nigra
Lamina iii,iv Nucleus propius
Lamina v Neck of posterior horn
Lamina vi Base of posterior horn
Lamina vii Intermediate zone,
intermediolateral horn
Lamina viii Commissural nucleus
Lamina ix Ventral horn
Lamina x Grisea centralis

REXED TERMINOLOGY
-laminae I to iv are exteroceptive sensation
- laminae v and vi proprioceptive
- lamina vii relay between midbrain and cerebellum
- lamina viii modulates motor activity, most probably via gamma neurons
-lamina ix is the main motor area of the spinal cord. It contains large alpha and smaller gamma motor
neurons
- alpha motor neurons in lamina ix are somatotopically organized, flexor muscle groups are located dorsally,
exensor muscle groups are located ventrally
SPINAL CORD DESCENDING TRACTS
TRACT NAME ORIGIN LOCATION EXTENT TERMINATION FUNC
Lateral corticispinal Contralateral Lateral Throughout Ipsilateral ventral Control of skilled movement,
cerebral cortex function spinal cord and dorsal horns modulation of sensory activity
Anterior cortcico- Ipsilateral Anterior Variable Contralateral ventral Control of skilled movement,
spinal (bundle of cerebral cortex funiculus and dorsal horns modulation of sensory activity
truck) (largely)
Tract of barnes Ipsilateral Lateral Throughout Ipsilateral ventral Control of skilled movement,
cerebral cortex function spinal cord and dorsal horns modulation of sensory activity
(largely)
robrospinal Contralateral Lateral Throughout Ipsilateral ventral Control of movement
cerebral cortex funiculus spinal cord horns
Lateral Ipsilateral Lateral Throughout Ipsilateral ventral Control of muscles that
vestibulospinal vestibular funiculus spinal cord horns maintain upright posture and
nucleus balance
Medial Ipsi- and Anterior Cervical spinal Ipsilateral ventral Head position in association
vestibulospinal contralateral funiculus cord horns with vestibular stimulation
medial
vestibular nuclei
reticulospinal Medullary and Lateral and Throughout Ipsilateral ventral Control of skilled movement,
pontine reticular Anterior spinal cord horns and modulation of sensory activity
formation, funiculus intermediate zone
bilaterally
Tectospinal Contralateral Anterior Cervical spinal Ipsilateral ventral Head posiition in association
superior funiculus cord horns with eye movement
colliculus
(midbrain)
Descending Ipsilateral Anterolater Throughout Ipsilateral Control of smooth muscles
autonomic hypothalamus al spinal cord intermediolateral cell and glands
funiculus column and sacral
pre-ganglionic cell
group
Moniaminergic Raphe nucleus, Lateral and Throughout Ipsilateral dorsal Control of pain transmission
locus ceruleus, Anterior spinal cord horns
periaqueductal funiculus
gray
NON SPECIFIC ASCENDING PATHWAY
- include the lateral and anterior spinothalamic tracts
- lateral; transmits impulses concerned with pain and temperature to opposite side of brain
- anterior: transmits impulses concerned with crude touch and pressure to opposite side of brain
- 1st order neuron : sensory neuron
- 2nd order neuron: interneurons of dorsal horn; synapse with 3rd order neurons in thalamus
- 3rd order neuron: carry impulse from thalamus to postcentral gyrus

BLOOD SUPPLY
-subclavian via the following branches: vertebral, ascending cervical, inferior thyroid, deep cervical, and
superior intercostal
-aorta via the following branches: intercostal and lumbar arteries
- internaliliac via the following branches:iliolumbar and lateral sacral

COMPLETE TRANSECTION
-with complete cord transection, all ascending tracts from below the level of the lesion and all descending
tracts from the above the level of the lesion are interrupted
- more often, the section is incomplete and irregular
- sensory- bilateral sensory loss below the level. In addition, there is a jhyperpathic zone at the border of the
lesion and for one or two dermatomes above it with complaints of pain of a burning character
- bladder/bowel - in the immediate and early stages following transection, all volitional or reflec functions of
the urinary bladder and bowel are lost, resulting in urinary and fecal retention. This may last from 8 days to
8 weeks. Subsequently, a state of automatic bladder emptying and intermittent reflex defecation develops.
- sexual - erection and ejaculatory functions are lost in males in the immediate and ealy stages. Later on,
reflex erection and ejaculation appear as a component of the automatic activity. In the female, there may be
temporary cessation of menstruation and irregularities in the menstrual cycle.

POSTERIOR COLUMN SYNDROMES

- selectively damaged by tabes dorsalis
- sensory ataxia, noted first at night or in dark, and a positive romberg’s sign
- lancinating (lightning) pains, most frequently in the legs, urinary incontinence, absent patellar, ankle
reflexes, hypotonic but not weak

ANTERIOR HORN CELL SYNDROME

- diffuse weakness, atrophy, and fasciculations, reuced muscle tone and reflex
- sensory changes are absent because the sensory tracts remain unaffected
- pure lower motor neuron syndromes have been described in cases of hexosaminidase deficiency,
poliomyelitis (postpolio syndrome), and post irradiation syndrome

CENTRAL LESION
- characteristically, the decussating fibers of the spinothalamic tract conveying pain and temperature
sensation are compromised initially
- because of the lamination oif the spinothalamic tract (dorsomedial cervical sensation and ventrolateral
sacral sensation), sacral sensation is spared (sacral sparing) by intraparenchymal lesions

POSTEROLATERAL COLUMN DISEASE

-onset often focal or predominantly unilateral muscle weakness or atrophy
- preogressive diffuse lower motor neuron signs (progressive muscular atrophy, paresis, and fasciculation)
are superimposed on the signs and symptoms of upper motor neuron dysfunction (paresis, spasticity, and
extensor plantar responses)

VASCULAR SYNDROMES

SYNDROME OF DORSAL ROOT GANGLION

-unpleasant stabbing pain and paresthesia dermatome level
- painful erythema followed by cutaneous vesicles
SYNDROME OF POSTERIOR ROOT
-sensation in the corresponding dermatome partially or totally lost, pain more affected
- hypotonia and hyporeflexia due to interruption of reflex arc

-
SYNDROME OF CORTICOSPINAL TRACTS
-primary lateral slecrosis and the rarer form of hereditarey spastic spinal paralysis
- initially of a feeling of a heaviness then weakness in the lower limbs
- spastic paraparesis with a spastic gait disturbance gradually develops and worsens. The reflexes are brisker
than normal
-spastic paresis of the upper limbs does not develop until much later

Syndrome of combined involvement

- spinocerebellar staxia of friedreich type, the axonal form of a hereditary neuropathy (NSMN II) and other
ataxias
- impairment of position sense, two-point discrimination and stereognosis, with spinal ataxia and a positive
romberg sign
- pain and temperature sense are largely or completely spared.

Extramedullary vs intramedullary lesions

Symptoms/ Intramedulla- ry Extramedulla- ry Tumors
Signs tumors
Radicular pain Unusual Common, may occur early
Vertebral pain Unusual Common
Funicular pain Common Less common
Upper motor neuron signs Yes, late Yes, early
Lower motor neuron signs Prominent and diffuse Unusual, if present, segmental distribution
Paresthesia’s progression Descending progression Ascending
Sphincter abnormalities Early with caudal lesions Late
(conuscauda equina)
Trophic changes common Unusual

LESSON
DESCENDING AND ASCENDING
GENERAL ORGANIZATION OF THE MOTOR SYSTEMS
 Upper motor neurons carry motor system outputs to lower motor neurons located in the spinal cord and
brainstem, which, in turn, project to muscles in the periphery. Descending upper motor neuron pathways
arise from the cerebral cortex and brainstem.
 These descending motor pathways can be divided into lateral motor system and medial motor system
based on their location in the spinal cord.
 Lateral motor systems travel in the lateral columns of the spinal cord and synapse on the more lateral
groups of ventral horn motor neurons and interneurons.
 Medial motor systems travels in the anteromedial spinal cord column to synapse on medial ventral horn
motor neurons and interneurons
 The two lateral motor systems are the lateral corticospinal tract anf the rubrospinal tract
 These pathways control the movement of the extremities
 The lateral corticospinal tract in particular is essential for rapid, dextrous movements at individual digits
or joints. Both of these pathways cross over from their site of origin and descend in the contralateral
lateral spinal cord to control the contralateral extremities
 The four medial motor sytstems are the anterior corticospinnal tract, the vestibulospinal tracts, the
reticulospinal tracts, and the tectospinal tract.
 These pathways control the proximal axial and girdle muscles involved in postural tone, balance,
orienting movements of the head and neck, and automatic gait-related movements
 The medial motor systems descend ipsilaterally or bilaterally. Some extend only to the upper few
cervical segments.
 The medial motor systems tend to terminate in interneurons that project to both sides of the spinal
cord, controlling movements that involved bilateral spinal segments
 Unilateral lesions of the medial motor systems produce no obvious deficits
 Lesion of the lateral corticospinal tract produce dramatic deficits
 The rubospinal tract in humans is small, and its clinical importance is uncertain, but it may participate
in taking over functions after corticospinal injury. It may also play a role in flexor (decorticate)
posturing of the upper extremities, which is typically seen with lesions above the level of the red
nuclei, in which the rubrospinal tract is spared.
Table 6.3. Lateral and Medial descending Motor Systems

Table 3-5. Spinal cord Ascending Tacts

LATERAL CORTICOSPINAL TRACT

 Most colinically important descending motor pathways in the nervous system.
 Controls movement of the extremities, and lesions along its course produce characteristic deficits that
often enable precide cliinical localization
 Over half of the corticospinal tract fibers originate in the primary motor cortex ( brodmann’s area 4)
of the precentral gyrus
 The remainder arise from the premotor and supplementary motor areas (area 6) or from the
parietal lobe ( areas 3 1 2 5 and 7)
 The primary motor cortex neurons contributing to the cortcospinal tract are located mostly in cortical
layer 5
 Layer 5 pyramidal cell projections synapse directly onto motor neurons in the ventral horn of the spinal
cord as well as onto spinal interneurons.
 About 3% of corticospinal neurons are giant pyramidal cells called betz cells, which are the largest
neurons in the human nervous system
Pic
 Axons from the cerebral cortex enter the upper portions of the cerebral white matter, or corona radiata
and descend toward the internal capsule
 The cerebral white matter conveys bidirectional information between different corticospinal areas and
between cortex and deep structures such as the basal ganglia, thalamus, and brainstem
 White matter pathways form a fanlike structure as they enter the internal capsule, which condenses
down to fewer and fewer fibers as connections to different subcortical structures are made
Pic
 Right and left internal capsule look like arrowheads or two letter vs. With their points facing inward
 The thalamus and caudate nucleus are always medial to the internal capsule, while the globus
pallidus and putamen are always lateral to the internal capsule
 There are three parts to the internal capsule: anterior limb, posterior limb, and genu
 Anterior limb of the internal capsule separates the head of the caudate from thr globus pallidus and
putamen, while the posterior limb separates the thalamus from the globus pallidus and putamen
 The genu (‘knee’ in latin) is at the transition between the anterior and posterior limbs, at the level of
the foramen of monro
 The corticospinal tract lies in the posterior limb of the internal capsule
 The somatotopic map is preserved in the internal capsule, so motor fibers for the face are most
anterior, and those for the arm and leg are progressively more posterior
 Fibers projecting from the cortex to the brainstem, including motor fibers for the face, are called
corticobulbar insted of corticospinal because they project from the cortex to the brainstem, or ‘bulb’.
 The fibers of the internal capsule are compact enough that lesions at this level often produce weakness
of the entire contralateral boy ( face, arm, and leg )
Pic
 The internal capsule continues into the midbrain cerebral peduncles, meaning, literally, ‘feet of the bran’
 The white matter is located in the ventral portion of the cerebral peduncles and is called the basis
pedunculi
 The middle one-third of the basis pedunculi contains corticobulbar and corticospinal fibers with the
face, arm, and leg axons arranged from medial to lateral, respectively
 The other portions of the basis pedunculi contain primarily corticopontine fibers
Pic
 The corticospinal tract fibers next descend through thr ventral pons, where they form somewhat
scattered fascicles.
 These collect on the ventral surface of the medulla to form the medullary pyramids
 For this reason the corticospinal tract is sometimes referred to as the pyramidal tract
 The transition from medulla to spinal cord is called the cervicomedullary junction, which occurs at the
level of the foramen magnum
 At this point about 85% of the pyramidal tract fibers cross over in the pyramidal decussation to enter
the lateral white matter columns of the spinal cord, forming the lateral corticospinal tract
Pic
RUBROSPINAL TRACT
 Neurons of origin of the rubrospinal tract are located in the magnicellular posterior two-thirds of the
red nucleus in the midbrain
 Fibers forming this tract cross in the ventral tegmental decussation of the midbrain and descend
throughout the whole length of the neuraxis to reach the lateral funiculus of the spinal cord in close
proximity to the corticospinal tract
 Terminate in the same laminae as the corticospinal tract and similarly facilitate flexor motor neurons
 Because of the similarity in the site of termination of both tracts and because the red nucleus receives an
input from the cortex, the rubospinal tract has been considered by some as an indirect corticospinal
tract
 The two tracts constitute the dorsolateral pathway for movement, in which the corticospinal tract
initiates movement and the rubrospinal corrects errors in movement
 In most mammals, the rubrospinal tract is the major output of the red nucleus
 The significance of the rubrospinal tract has diminished with evolution. In humans, the major output of
the red nucleus is to the inferior olive.
LATERAL VESTIBULOSPINAL TRACT
 The neurons of origin of this tract lie in the lateral vestibular nucleus located in the pons.
 Fibers descend uncrossed and occupy a position in the lateral funiculus of the spinal cord
 The fibers in this tract terminate on interneurons in laminae VII and VIII, with some direct terminations
on alpha motor neuron dendrites in the same laminae
 The impulses conducted in this system facilitate extensor motor neurons that maintain upright posture.
Pic
MEDIAL VESTIBULOSPIANL TRACT
 The neurons of origin of the medial vestibulospinal tract are located In the medial vestibular nucleus
 From their neurons of origin, fibers join the ipsilateral and contralateral medial longitudinal fasciculus,
descend in the anterior funiculus of the cervical cord segments, and terminate on neurons in laminae VII
and VII
 They exert a facilitatory effect on flexor motor neurons. The tracts plays a role in control of head
position.
RETICULOSPINAL TRACTS
 The neurons of origin of these tracts are located in the reticular formation of the pons and medulla
oblongata
 The pontine reticulospinal tract is located in the anterior funiculus of the spinal cord, whereas the
medullary reticulospinal tract is located in the laeral funiculus
 Both tracts descend predominantly ipsilaterally, but both have, in addition, some crossed components
 The pontine reticulospinal tract facilitatees extensor motor neurons, whereas the medullary
reticulospinal tract facilitates flecor motor neurons
 Pontine originating fibers terminate in laminae VII and VII of rexed, whereas medullary originating
fibers terminate primarily in lamina VII
 Some medullary originating fibers interact with motor neuron dendrites in laminae VII and VII
 In addition to influencing motor neurons, reticulospinal fibers modify sensory activity through their
interaction withe spinothalamic neurons in the dorsal horn.

TECTOSPINAL TRACT
 From their neurons of origin in the superior colliculus of the midbrain, fibers of this tract cross in the
dorsal tegmental decussation in the midbrain in the midbrain and descend throughout the neuraxis to
occupy a position in the anterior funiculus of the cervical spinal cord
 Fibers of this tract terminate in neurons in laminae VI, VII, and VIII
 The function of this tract is not well understood; it is believed to play a role in the turning of the head
in response to light stimulation

ASCENDING TRACTS
DORSAL SPINOCEREBELLAR TRACT
 Conveys to the cerebellum proprioceptive impulses from receptor located in muscles, tendons, and
joints
 The impulses arising in muscle spindles travel via Ia and II nerve fibers, whereas those arising in golgi
tendon organs travel via lb nerve fibers
 Central processes of neurons in dorsal root ganglia enter the spinal cord via the dorsal root and either
ascend or descend in the posterior funiculus for a few segments before reaching the spinal nucleus, or
they may reach the nucleus, or they may reach the nucleus directly
 Nerve cells, the axons of which form this tract, are located in the nucleus dorsalis of clarke (also
knoown as clarke’s column, nucleus thoracicus, thoracic nucleus, stilling column, stilling nucleus)
within lamina VII of rexed
 This nucleuss is not found throughout the extent of the spinal cord but is limited to the spinal cord
segments between the eight cervical ( C-8) and second lumbar ( L-2)
 The dorsal spinocerebellar tract is not seen below the second lumbar segment
 Nerve fibers belonging to this system and entering below L-2 ascend to the L-2 level, where they
synapse with cells located in the nucleus
 Nerve fibers entering above the upper limit of the nucleus ascend in the cuneate tract to reach the
accessory cuneate nucleus in the medulla oblongata, which is homologous to the nucleus dorsalis.
 Fibers in this tract are segmentally laminated in such ways that fibers from lower limbs are place
superficially
 The fibers in this tract reach the cerebellum via the inferior cerebellar peduncle (restiform body) and
terminate on the rostal and caudal portion if the vermis.
 The dorsal spinocerebellar tract conveys to the cerebellum information pertaining to muscle contraction,
including phase, rate, and strength of contraction
 There is evidence to suggest that some of the fibers forming this tract arise from neurons in laminae V
and VI of rexed, as well as from the nucleus dorsalis of clarke.
A. Unconscious proprioception

POSTERIOR COLUMN-MEDIAL LEMNISCAL PATHWAY

 Large-diameter, myelinated axons carrying information about proprioception, vibration sense, and
fine touch enter the spinal cord via the medial portion of the dorsal root entry zone
 Many of these axons then enter the ipsilateral posterior columns to ascend all the way to the posterior
column nuclei in the medulla
 Some axxon collaterals enter the spinal cord central grat matter to synapse onto interneurons and motor
neurons
 It is easier to remember the somatotopic organization of the posterior columns of you picture fiberes
adding on laterally from higher levels as the posterior column ascend
 Medial portion, called the gracile fasciculus ( gracile mean ‘thin’) carries information from the legs and
lower trunk
 The more lateral cuneate fasciculus (cuneate meas ‘wedge shaped’) carries information from the upper
trunk above the T6, and from the arms and neck
 The first-order sensory neurons that have axons in the gracile and cuneate fasciculus (also called
fasciculus gracillis and fasciculus cuneatus) synapnse onto second0order neurons in the nucleus gracilis
and nucleus cuneatus, respectively
 Axons of these second-order neurons decussate as internal arcuate fibers and then form the medial
lemniscus on the other side of the medulla
 The medial lemniscus initially has a vertical orientation and then comes to occupy a progressively more
lateral and inclined position as it ascend in the brainstem
 The somatotopic organization of the medial leminiscus assumes a vertical position in the medulla such
that the feet are represented more ventrally (‘ the little person stand up’) and then inclines again in the
pons and midbrain such that the arms are represented more medially and legs are more laterally ( ‘the
little lies down’)
 Note the reversal in somatotopic orientation; for the medial lemniscus in the pons and midbrain the
feet are lateral, while in posterior columns the feet are medial. Recall that most somatotopic maps
represent the upper body medially and lowe body laterally, with the notable exceptions of the posterior
columns and primary sensory-motor cortices
 The next major synapse occurs when the medial lemniscus axons terminate in the ventral posterior
lateral nucleus (VPL) of the thalamus
 The neurons of the VPL then project through the posterior limb of the internal capsule in the
thalamicsensorycortex radiations to reach the primary somatosensorycortex (areas 3, 1,2 ) in the
postcentral gyrus
 Synaptic inputs to the primary somatosensory cortex from both the face and body occur mainly in
cortical layer IV and the deep portions of layer III, with some inputs also reaching layer VI
Pic
LATERAL SPINOTHALAMIC TRACT
 Smaller-diameter and unmyelinated axons carrying information about pain and temperature sense also
enter the spinal cord via the dorsal root entry zone
 These axons make their first synapses immediately in the gray matter of the spinal cord, mainly in the
dorsal horn marginal zone (lamina I) and deeper in the dorsal horn, lamina V
 Some axon collaterals ascend or descend for a few segments in lissauer’s tract before entering the
central gray
 Axons from the second-order sensory neurons in the central gray cross over the spinal cord anterior
(ventral) commissure to ascend in the anterolateral white matter
 It should be noted that it takes two to three spinal segments for the decussating fibers to reach the
opposite side, so a lateral cord lesion will affect contralateral pain and temperature sensation beginning
a few segments below the level of the lesion
 The anterolateral pathways in the spinal cord have a somatotopic organization in which the feet are most
laterally represented
 Somatotopic organization, with arms more medial and legs more lateral, is preserved as the anterolateral
pathways pass through the brainstem
 When they reach the medulla, the anterolateral pathways are located laterally, running in the groove
between the inferior olives and the inferior cerebellar peduncles. They then enter the pontine tegmentum
to lie just lateral to the medial lemniscus in the pons and midbrain

Table 8.1 Summary of Peripheral Nerves, Muscles, and Nerve Roots in the Upper and Lower Extremities

NERVE MUSCLES FUNCTION OF THE NERVE ROOTS

MUSCLE(S)

Spinal accessory nerve Trapezius Elevates shoulder/ arm and CN XI, C3, C4
fixes scapula

Phrenic nerve Diaphragm Inspiration C3, C4, C5

Dorsal scapular nerve Rhomboids Draw scapula up and in C4, C5

Levator scapulae Elevates scapula C3, C4, C5

Long (Bell’s) thoracic nerve Serratus anterior Fixes scapula on arm raise C5, C6, C7

Lateral pectoral nerve Pectoralis major (clavicular Pulls shoulder forward C5, C6
head)

Medial pectoral nerve Pectoralis major (sternal Adducts and medially rotates C6, C7, C8, T1
head) arm

Pectoralis minor Depresses scapula and pulls C6, C7, C8

shoulder forward
Suprascapular nerve Supraspinatus Abducts humerus from 0 C5, C6
degrees to 15 degrees

Infraspinatus Externally rotates humerus C5, C6

Subscapular nerve Subscapularis Internally rotates humerus C5, C6

Adducts and internally rotates

Teres major humerus C5, C6, C7
Thoracodorsal nerve Latissimus dorsi Adducts and internally rotates C6, C7, C8
humerus

Axillary nerve Teres minor Adducts and externally rotates C5, C6

humerus
 Deltoid Abducts humerus beyond 15 C5, C6
degrees
Musculocutaneous nerve Biceps brachii Flexes and supinates arm and C5, C6
forearm

Brachialis Flexes forearm C5, C6

Coracobrachialis Flexes and adducts arm C6, C7

Radial nerve Triceps Extends forearm C6, C7, C8

Brachioradialis Flexes forearm C5, C6

Extensor carpi radialis Extend wrist, abduct hand C5, C6

(longus and brevis)
Posterior interosseus nerve Supinator Supinates forearm C6, C7
(branch of radial nerve)
Extensor carpi ulnaris Extends wrist, adducts hand C7, C8

Extends fingers (test at

Extensor digitorum communis metacarpophalangeal joints) C7, C8

Extends little finger

Extensor digiti quinti
Abducts thumb in plane of C7, C8
Abductor pollicis longus palm
C7, C8
Extends thumb
Extensor pollicis (longus and
brevis) C7, C8
Extends index finger
Extensor indicis proprius
C7, C8

Median nerve Pronator teres Pronates and flexes forearm C6, C7

Flexes wrist, abducts hand

Flexor carpi radialis C6, C7
Flexes wrist

Palmaris longus Flexes metacarpophalangeal C7, C8, T1

and proximal interphalangeal
Flexor digitorum superficialis joints C7, C8, T1

For second and third digits,

flexes metacarpophalangeal
Lumbricals (I, II) joints, extends other joints
C8, T1
Flexes, opposes thumb

Abducts thumb perpendicular

to plane of palm
Opponens pollicis
C8, T1
Abductor pollicis brevis Flexes first phalanx of thumb
C8, T1

Flexor pollicis brevis

C8, T1
Muscles affected in carpal
tunnel syndrome

Anterior interosseous nerve Flexor digitorum profundus Flexes second and third C7, C8
(branch of median nerve) (digits 2,3) fingers (best tested in distal
phalanges)

Flexor pollicis longus Flexes distal phalanx of C7, C8

thumb

Pronator quadratus Pronates forearm C7, C8, T1

Ulnar nerve Flexor carpi ulnaris Flexes wrist, adducts hand C7, C8, T1

Flexes fourth and fifth fingers

 Flexor digitorum profundus (best tested and distal C7, C8
(digits 4,5) phalanges)

For fourth and fifth digits,

Lumbricals (III, IV) flex metacarpophalangeal C8, T1
joints, extend other joints

Adduct fingers, flex

metacarpophalangeal joints,
extend other joints
Palmar interossei C8, T1
Abduct fingers, flex
metacarpophalangeal joints,
extend other joints

Dorsal interossei Flexes and adducts thumb C8, T1

Adducts thumb

Internally rotates fifth finger

Flexor pollicis brevis (deep C8, T1
head) Abducts fifth finger

Adductor pollicis Flexes fifth finger at C8, T1

metacarpophalangeal joint
Opponents digiti minimi C8, T1

Abductor digiti minimi C8, T1

Flexor digiti minimi C8, T1

Muscles of hypothenar
eminence
Obturator nerve Obturator externus Adducts and outwardly L2, L3, L4
rotates leg

Adductor longus Adducts thigh L2, L3, L4

Adductor magnus Adducts thigh L2, L3, L4

Adductor brevis Adducts thigh L2, L3, L4

Femoral nerve Gracilis Adducts thigh L2, L3, L4

Iliacus Flexes leg at hip L1, L2, L3

Psoas Flexes leg at hip L2, L3, L4

Iliopsoas muscle

Rectus femoris Extends leg at knee, flexes hip L2, L3, L4

Extends leg at knee

Vastus lateralis L2, L3, L4
Extends leg at knee
Vastus intermedius L2, L3, L4
Extends leg at knee
Vastus medialis L2, L3, L4

Quadriceps femoris
Adducts thigh
Pectineus L2, L3, L4
Inwardly rotates leg, flexes
Sartorius hip and knee L2, L3, L4
Sciatic nerve Adductor magnus Adducts thigh L4, L5, S1

Semitendinosus Flexes knee, medially rotates L5, S1, S2

thigh, extends hip

Flexes knee, medially rotates

Semimembranosus thigh, extends hip L5, S1, S2
 Flexes knee, extends hip

Biceps femoris L5, S1, S2

Hamstring muscles
Tibial nerve (branch of sciatic Gastrocnemius Plantar flexes foot S1, S2
nerve)
Soleus Plantar flexes foot S1, S2

Triceps surae muscles

Popliteus Plantar flexes foot L4, L5, S1

Tibialis posterior Plantar flexes and inverts foot L4, L5

Spreads, brings together,

Plantaris flexes proximal phalanges L4, L5, S1

Flexes distal phalanges, aid

plantar flexion
Flexor digitorum longus L5, S1, S2
Flexes great toes, aids plantar
flexion
Flexor hallucis longus L5, S1, S2
Cup sole

Small foot muscles S1, S2

TABLE 6.3 Lateral and Media Descending Motor Systems

TRACT SITE OF ORIGIN SITE OF LEVELS OF FUNCTION

DECUSSATION TERMINATION
(WHERE
RELEVANT)
LATERAL MOTOR SYSTEMS

Lateral Corticospinal Primary motor cortex Pyramidal decussation, Entire cord (pre- Movement of
Tract and other frontal and at the cervicomedullary dominantly at cervical contralateral limbs
parietal areas junction and lumbosacral
enlargements)
Rubrospinal Tract Red nucleus, Ventral tegmental Cervical cord Movement of
magnocellular division decussation, in the contralateral limbs
midbrain (function is uncertain in
humans)
MEDIAL MOTOR SYSTEM

Anterior corticospinal Primary motor cortex _____________ Cervical and upper Control of bilateral
tract and supplementary thoracic cord axial and girdle
motor area muscles
Vestibulospinal tracts Medial VST: medial ______________ Medial VST: Cervical Medial VST:
(VsT) and inferior vestibular and upper thoracic positioning of head and
nuclei; lateral VST: cord; Lateral VST; neck; lateral VST:
lateral vestibular entire cord balance
nucleus
Reticulospinal tracts Pontine and medullary ______________ Entire cord Automatic posture and
reticular formation gait-related movements
Tectospinal tract Superior colliculus Dorsal tegmental Cervical cord Coordination of head
decussation, in the and eye movement
midbrain (uncertain in humans)
Despite their names, both medial and lateral VSTs are medial motor systems.

Table 3-5. Spinal Cord Ascending Tracts

Tract name Origin Location Extent Termination Function

Gracile Ipsilateral dorsal Medial in posterior Throughout spinal Ipsilateral gracile Conscious
root ganglion funiculus cord nucleus in medulla proprioception

Cuneate Ipsilateral dorsal Lateral in posterior Above sixth Ipsilateral cuneate Conscious
root ganglion funiculus thoracic segment nucleus in medulla proprioception

Dorsal Ipsilateral nucleus Lateral funiculus Above second Ipsilateral Unconscious

spinocerebellar dorsalis of Clarke lumbar segment cerebellum proprioception

Ventral Contralateral Lateral funiculus Throughout spinal Contralateral Unconscious

spinocerebellar dorsal horn cord cerebellum proprioception

Spinocervical Ipsilateral dorsal Lateral funiculus Throughout spinal Ipsilateral lateral Conscious
thalamic (Morin’s) root ganglion cord cervical nucleus proprioception

Lateral Contralateral Lateral funiculus Throughout spinal Ipsilateral thalamus Pain and thermal
Spinothalamic dorsal horn cord (ventral sensations
posterolateral
nucleus)
Anterior Contralateral Lateral and anterior Throughout spinal Ipsilateral thalamus Light touch
spinothalamic (largely) dorsal funiculi cord (ventral
horn posterolateral
nucleus)

 Motor neuron disorders (can also cause lower

COMMON NEUROPATHIES
 Neuropathy is a general term meaning nerve
disorder.
 The site of pathology can be in the
axons,myelin, or both and can affect large-
diameter fibers, small-diameter fibers, or both.
 Usually, neuropathies affect both sensory and
motor fibers in the nerve, although one or the
other may be preferentially involved.
 Damaged can be reversible or permanent.
 The local of neuropathy can be focal
(mononeuropathy), multifocal
(mononeuropathy multiplex), or generalized
(polyneuropathy).
 Neuropathy affecting the spinal nerve roots is
called radiculopathy
motor neuron-type weakness but motor neuron
disorders do not cause sensory involvement.
 Important causes of neuropathy:
1. Diabetes
2. Mechanical causes
3. Infectious disorders such as Lyme disease,
HIV, CMV, vericella-zoster virus, or
hepatitis B
4. Toxins
5. Malnutrition
6. Immune disorders such as Guillain-Barre
syndrome
7. Hereditary neuropathies such as Charcot-
Marie-Tooth disease, among others.
Diabetic Neuropathy
 Produced by a number of mechanisms,
including compromise of the microvascular
blood supply of the peripheral nerves (other
 possible mechanisms include oxidative stress,
autoimmunity, and neurotrophic and
biochemical disturbances).
 The most common pattern of diabetic
neuropathy is distal symmetrical
polyneuropathy, which results in a
characteristic glove and stocking pattern of
sensory loss
 Mononeuropathies are also relatively common
in diabetes.
 Acute diabetic mononeuropathy can affect any
cranial or spinal nerve but is most common in
CN III and the femoral and sciatic nerves.
 Onset is usually fairly sudden, and
sensorimotor deficits in the nerve distribution
may be accompanied by painful paresthesias.
 There is often partial or complete recovery over
the course of weeks to months after onset.
Mechanical causes of nerve injury
 Include extrinsic compression, traction,
laceration, or entrapment by intrinsic structures
such as bone or connective tissue.
 Mild mechanical disruption of a nerve causes
neurapraxia, temporary impairment of nerve
conduction that usually resolves within hours to
weeks.
 More severe injury can interrupt the axons,
leading to Wallerian degeneration
(degeneration of axons and myelin) distal to
the site of injury.
 As long as the structural elements of the nerve
are intact, axonal regeneration may occur at a
rate of about 1 mm/day (a little more than 1
in./month).
 Occasional long-term complications include
incomplete or aberrant reinnervation and the
complex regional pain syndrome.
 Complex regional pain syndrome Type 1, also
called reflex sympathetic dystrophy, is more
common and follows an injury without specific
nerve damage, while Type 2, also called
causalgia, follows damage to a specific nerve.
 Both types are characterized by intense local
burning pain accompanied by edema, sweating,
and changes in skin blood supply.
 In some situations, when peripheral nerves are
severed or otherwise disrupted they can be
reanastomosed surgically.
 In addition, some entrapment syndromes may
be amenable to surgical decompression.
 Painful paresthesias associated with
neuropathies of all causes are often treated with
medications such as anticonvulsants, serotonin-
norepinephrine reuptake inhibitors, or tricyclic
antidepressants.
 Occasional long-term complications include
incomplete or aberrant reinnervation and the
complex regional pain syndrome.
 Complex regional pain syndrome Type I, also
called reflex sympathetic dystrophy, is more
common and follows an injury without specific
nerve damage, while Type 2, alo called
causalgia, follows damage to a specific nerve.
 Both types are characterized by intense local
burning pain accompanied by edema, sweating,
and changes in skin blood supply.
Guillain-Barre syndrome
 Acute inflammatory demyelinating
polyneuropathy (AIDP), is an important form
of neuropath caused by immune-mediated
demyelination of peripheral nerves.
 Onset typically occurs 1 to 2 weeks following a
viral illness, Campylobacter jejuni enteritis,
HIV infection, or other infections.
 Presentation is with progressive weakness,
areflexia, and tingling paresthesias of the hands
and feet, with motor involvement typically
much more severe than sensory involvement.
 Symptoms usually reach their worst point 1 to
3 weeks after onset; recovery occurs over many
months
 Diagnosis is based on typical clinical
presentation, cerebrospinal fluid (CSF)
demonstrating elevated protein without a
significantly elevated white blood cell count,
and EMG/nerve conduction studies compatible
with demyelination
 Recovery occurs more quickly when patients
are treated with plasmapheresis or intravenous
immunoglobulin therapy.
 In severe cases, patients require intubation and
mechanical ventilation.
 Autonomic dysfunction can be prominent in
some cases, requiring careful monitoring. With
good supportive care and immune therapy, the
majority of patients enjoy complete or near-
complete recovery, although about 20% of
patients have some residual weakness 1 to year
after onset.
Common Disorders of the Neuromuscular
Junction
 Myasthenia gravis is an immune-mediated
disorder in which there are circulating
antibodies against the postsynaptic nicotinic
acetylcholine receptors at the neuromuscular
junction of skeletal muscle cells.
 The disorder can sometimes be accompanied
by other autoimmune phenomena such as
hypothyroidism, lupus, rheumatoid arthritis,
and vitiligo.
 Myasthenia gravis has a bimodal age-related
onset, with onset in the second or third
decades more common in woman and onset
in the sixth or seventh decades more common
in men.
 The prevalence is 50 to 125 cases per million.
 Clinical features include generalized
symmetrical weakness, especially of proximal
limb muscles, neck muscles the diaphragm, and
eye muscles. Involvement of bulbar muscles
can cause facial weakness, a nasal-sounding
voice, and dysphagia
 Reflexes and sensory exam are normal.
 Characteristically, weakness becomes more
severe with repeated use of a muscle or during
the course of the day.
 About 15% of cases have weakness involving
only the extraocular muscles and eyelids, a
condition called ocular myasthenia.
Myasthenia gravis
 Diagnosis of myasthenia gravis is based on
clinical features, and several diagnostic tests,
including the ice pack test, repetitive nerve
stimulation, measurement of anti-
acetylcholine antibodies or muscles specific
receptor tyrosine kinase (MuSK) antibodies,
single fiber EMG, and chest CT or MRI.
 The ice pack test, which can be performed in
patients with ptosis, is administered by placing
a bag of ice on the closed eyelids for 2 minutes,
and reevaluating for improvement in the ptosis
(possibly due to reduced cholinesterase
function at lower temperature).
 Tensilon test, using a short-acting
acetylcholinesterase inhibitor (edrophonium)
was administered at bedside while observing
clinical effects on involved muscles.
 Commercial manufacturer of this agent was
discontinued in 2008, however, making future
availability of this test uncertain.
 Clinical response to intermediate-acting
acetylcholinesterase inhibitors, such as
neostigmine, may also be diagnostically
helpful in some cases.
 Compound motor action potential measurement
(see KCC 9.2) with repetitive nerve stimulation
at a rate of 3 second often produces a
characteristic decrement in amplitude in
myasthenia and is considered positive if there
is a decrement greater than 10%.
 Single-fiber EMG is more sensitive (about
90%) but is not specific for myasthenia.
 About 12% of patients with myasthenia have a
thymoma, a tumor of the thymus gland, and
many others have thymic hyperplasia, so CT or
MRI of the chest should be performed.
 Testing for associated conditions such as
thyroid disease and other immune disorders is
appropriate.
 Myasthenia gravis is treated by immune
therapy.
 Anticholinesterase medications are also helpful
to relieve symptoms.
 Pyridostigmine (Mestinon) is a long-acting
cholinesterase inhibitor,with onset of action
beginning about 30 minutes after oral
administration and duration of about 2 hours.
 Patient’s doses are individually titrated but
should not ordinarily exceed about 120 mg
every 3 hours, since excess anticholinesterase
can actually worsen weakness.
 Most patients in the age range of adolescence
to 60 years are treated surgically with
thymectomy (whether a thymoma is present or
not), as this usually leads to improvement by
unclear mechanisms, likely involving a reduced
autoimmune response.
 Use of thymectomy outside this age range or in
patients with ocular myasthenia is more
controversial but has been used in some cases.
 Thymectomy should be performed at a time
when patients are relatively clinically stable in
order to minimize complications in the
perioperative period.
 Short-term immunotherapy with
plasmapheresis or intravenous immune
globulin (IVLg) can be helpful, particularly
when patients are in myasthenic crisis requiring
intubation, experiencing other severe
worsening in symptoms, or in preparation for
elective surgery.
 Longer-term immunosuppressive agents,
including steroids, azathioprine,
mycophenolate and cyclosporine, are also
typically prescribed.
Common Muscle Disorders
 Muscle disorders, or myopathies, produce
weakness that is typically more severe
proximally than distally, without loss of
sensation or reflexes.
 Common causes of myopathy include thyroid
disease, malnutrition, toxins, viral infections,
dermatomyositis, polymyositis, and muscular
dystrophy.
 Dermatomyositis and polymyositis are
immune-mediated inflammatory myopathies.
 The blood creatinine phosphokinase (CPK) is
typically elevated, and electromyography
(EMG) studies are compatible with myopathy.
Radiculopathy
 Sensory or motor dysfunction caused by
pathology of a nerve root is called
radiculopathy.
 Radiculopathy is often associated with a
burning, tingling pain that radiates or shoots
down a limb in the dermatome of the affected
nerve root.
 There may be loss of reflexes and motor
strength in a radicular distribution
 Chronic radiculopathy can result in atrophy and
fasciculations
 Sensation may be diminished if a single
dermatome is involved, but because of overlap
from adjacent dermatomes, sensation is usually
not absent.
 Testing with pinprick is more sensitive than
touch for detecting radicular sensory loss.
 Relatively mild or recent-onset radiculopathy
can cause sensory changes without motor
deficits.
 T1 radiculopathy can interrupt the sympathetic
pathway to the cervical sympathetic ganglia,
resulting in Horner’s syndrome.
 Involvement of multiple nerve roots below L1
can result in a cauda equina syndrome
 The most common cause by far is intervertebral
disc herniation, which occurs part of all of the
nucleus pulposus extrudes through a tear in the
annulus fibrosus, often causing root
compression
 It usually occurs without any recent history of
traumatic injury, but it can occasionally be
caused or exacerbated by trauma.
 Disc herniation as a cause of radiculopathy is
common for the C6, C7, L5, and S1 nerve roots
and less common at other levels.
 Lumbosacral radiculopathies are about two to
three times as common as cervical
radiculopathies
 Thoracic disc herniation are less common,
since this region of the spinal column is less
mobile and fixed by the rib cage.
 Patients with intervertebral disc herniation
typically present with back or neck pain, as
well as sensorimotor symptoms in a radicular
distribution.
 As the spine degenerates over time, bony
osteophytes form
 Osteophytes, together with disc material, may
contribute to narrowing of the intervertebral
foramina or may protrude more centrally into
the canal, causing spinal stenosis and chronic
injury to the spinal cord (myelopathy).
Cauda Equina Syndrome
 Impaired function of multiple nerve roots
below L1 or L2 is called cauda equina
syndrome.
 If the deficits begin at the S2 roots and below,
there may be no obvious leg weakness.
 Sensory loss in an S2, S3, and S4 nerve roots
can produce a distended atonic bladder with
urinary retention or overflow incontinence,
constipation, decreased rectal tone, fecal
incontinence, and loss of erections.
 It is essential to detect and treat cauda equina
syndrome promptly to avoid irreversible
deficits.
 Cauda equina syndrome can sometimes be
difficult to differentiate from conus medullaris
syndrome, in which similar deficits occur as the
result of a lesion in the sacral segments of the
spinal cord.
 Causes of cauda equina syndrome include
compression by a central disc herniation,
epidural metastases, schwannoma,
meningioma, neoplastic meningitis, trauma,
epidural abscess, arachnoiditis, and
cytomegalovirus polyradiculitis.
Common causes of Radiculopathy
Disc herniation
Osteophytes
Spinal stenosis
Trauma
Diabetes
Epidural abscess
Epidural metastases
Meningeal carcinomatosis
Nerve sheath tumors (schwannomas and
neurofibromas)
Guillain-Barre syndrome
Herpes zoster (shingles)
Lyme disease
Cytomegalovirus
Idiopathic neuritis
 Differential Diagnosis of Back Pain
Trauma/ mechanical Disc herniation; spondylolysis; vertebral fracture; arthritis; muscle
strain/ ligament sprain; soft tissue injury
Vascular Spinal arteriovenous malformation; spinal cord infarct; subarachnoid
hemorrhage; spinal epidural hematoma
Infectious/ Osteomyelitis; arachnoiditis; spinal epidural abscess; myositis;
inflammatory/ cytomegalovirus radiculitis; muscle aches in viral illness; Guillain-
neoplastic Barre syndrome; primary or metastatic neoplasms (extradural,
extramedullary, or intramedullary).
Degenerative/ Scoliosis; degenerative joint disease; amyotrophic lateral sclerosis
developmental
Referred/ other (non- Normal pregnancy; ectopic pregnancy; menses; urinary tract
neurologic infection; pyelonephritis; renal stone; retroperitoneal abscess;
retroperitoneal hematoma; retroperitoneal tumor; pancreatitis; aortic
aneurysm; aortic dissection; angina; myocardial infarction;
pulmonary embolism

Clarifying Definitions for Degenerative Disorders of the Spine

Disorder Definition
Spondylolysis A general term for degenerative disorders of the spine. From greek
spondylos, meaning “vertebra”.
Spondylolysis Fractures that appear in the interarticular portion of the vertebral
bone, between the facet joints. Lysis means “loosening” in Greek.
spondylolisthesis Displacement of a vertebral body relative to the vertebral body
beneath it. Includes anterolisthesis or retrolisthesis, meaning
“anterior” or “posterior” displacement of the upper vertebral bone,
respectively. Anterolisthesis often coexists with spondylolysis. In
Greek, olisthesis means “slipping and falling”.
Osteophytes Bony spurs that form on regions of apposition between adjacent
vertebrae because of chronic degeneration. From the Greek osteo,
meaning “bone”, plus phyton, meaning “plant” or “outgrowth”.
Spinal Stenosis Congenital or acquired narrowing of the spinal canal.
 SOMATOSENSORY PATHWAYS carries information into the spinal cord
 The term somatosensory generally refers to through the dorsal nerve roots.
body sensations of touch, pain, temperature,  A peripheral region innnervated by sensory
vibration, and proprioception (limb or joint fibers from a single nerve root level is called
position sense). There are two main dermatome.
pathways for somatic sensation:
 The posterior column-medial lemniscal SOMATOSENSORY CORTEX
pathway conveys proprioception,  From the thalamic VPL and VPM nuclei,
vibration sense, and fine, discriminative somatosensory information is conveyed to the
touch. primary somatosensory cortex in the
 The anterolateral pathways include the postcentral gyrus which includes Brodmann’s
spinothalamic tract and other associated areas 3,1,2
tracts that convey pain, temperature  Somatotopically organized, with the face
sense, and crude touch. represented most laterally and the leg most
 Four types of sensory neuron fibers are medially
classified according to axon diameter  Information from the primary somatosensory
 These different fibers types have specialized cortex is conveyed tp the secondary
peripheral receptors that subserve different somatosensory association cortex located
sensory modalities. within the sylvian fissure, along its superior
 Large-diamter, myelinated axons conduct margin in a region called the parietal
faster than smaller-diamter or unmyelinated operculum.
axons.  The secondary somatosensory cortex is also
organized somatotopically
 Further processing of somatosensory
Table7.2. sensory neuron fiber types
information occurs in association cortex of
Nam Altern Fiber Myelin Receptor Sensory
e ate diame ated modalities the posterior parietal lobule, including
name ter brodmann’s areas 5 and 7
A-α I 13- Yes - Muscle -Proprioce  Primary somatosensory cortex and
20 spindle ption somatosensory association cortex alos have
- Golgi -proprioce extensive connections with the motor cortex.
tendon organ ption
 Lesions of the somatosensory cortex and
A- β II 6-12 Yes - muscle - proprioce
adjacent regions produce characteristic
spindle ption
- meissner’s - superficial deficits referred to as cortical sensory loss.
corpuscle Touch
-merkel’s - superficial CENTRAL MODULATION of PAIN
receptor Touch  Pain, modulation involves interactions
- pacinian - deep touch, between local circuits at the level of the
corpuscle Vibration spinal cord dorsal horn and long-range
- ruffini - deep touch, modulatory inputs
ending Vibration  Gate control theory, sensory inputs from
- hair - touvh, large-diamter, nonpain A- β fibers reduce pain
receptor vibration
transmission through the dorsal horn.
A-δ III 1-5 Yes - bare nerve - pain
Ending  For example, transcutaneous electrical nerve
- bare nerve -tempera- stimulation (TENS) devices work to reduce chronic
Ending ture (cool) pain by activating A- β fibers. This is also why
-bare nerve - Itch shaking your hand after striking your numb with a
ending hammer temporarily helps relieve the pain.
C IV 0.2- No - bare nerve - pain  The periaqueductal gray receives inputs from
1.5 Ending the hypothalamus, amygdala, and cortex, and
- bare nerve - termpera- it inhibits pain transmission in the dorsal forn
Ending ture (warm)
via a relay in a region at the pontomedullary
- bare nerve - itch
ending junction called rostal ventral medulla (RVM)
 This region includes serotonergic (5-HT)
neurons of the raphenuclei that projects to
 Sensory neuron cell bodies are located in the spinal cord, modulating pain in the dorsal
the dorsal root ganglia horn
 Each dorsal root ganglion cell has a stem  The RVM also sends input mediated by the
axon that bifurcates, resulting in one long neuropeptide substance P to the locus
process that conveys sensory information from ceruleus, which in turn sends noradrenegic
the periphery and a second process that
 (NE) projections to modulate pain in the
spinal cord dorsal horn.
Central Modulation of Pain
 Opiate medications such as morphine are
likely to exert their analgesic effects
through receptors found in widespread
locations throughout the nervous system,
including receptors located on peripheral
nerves and neurons in the spinal dorsal
horn.
 Opiate receptors and endogenous opiate
peptides such as enkephalin, B-endorphin,
and dynorphin, are found in particularly
high concentrations at key points in the
pain modulatory pathways.
 Enkephalin- and dynorphin-containing
neurons are concentrated in the
periaqueductal gray, RVM, and spinal cord
dorsal horn, while B-endorphin-containing
neurons are concentrated in regions of the
hypothalamus that project to the
periaqueductal gray.
RECEPTOR ORGANS OF SENSORY NEURONS
Sensory receptors may be classified:
 By function for example, nociceptor (pain)
or mechanoreceptor
 By structure, for example, encapsulated or
nonencapsulated (so-called free)
 By a combination of both structure and
function
 By anatomic location, for example
exteroceptors (skin receptors),
proprioceptors (muscle, tendon, joint
receptors), and visceroceptors (receptors
in internal body organs.)
 Sensory receptors provide information
about the location, intensity, and duration
of peripheral stimulus.
 They are designed to change (transduce)
one kind of energy to another (i.e., touch
to electrochemical nerve impulse)
 Each receptor possesses a different
sensitivity and different adaptive
properties based on its response to
continuous monotonic stimulation.
 Receptors may adapt quickly or slowly.
 Quickly (fast) adapting receptors (phasic
receptors) produce impulse that gradually
decrease in strength in response to
constant and unvarying stimuli.
 Slowly adapting receptors (tonic receptors)
continue their response level throughout
their activation and the duration of
stimulation.
 Fast adapting receptors thus detect
transient and rapidly changing stimuli,
whereas slow adapting receptors detect a
sustained stimulus.
 Slowly adapting receptors are of two
types:
 Type I receptors have no
spontaneous discharge at
rest and more sensitive to
vertical displacement.
 Type II receptors maintain a
slow regular discharge at
rest and more sensitive to
stretch.
 FREE (NONENCAPSULATED) NERVE
ENDINGS
 are the axonal endings designed for
sensory reception
 widest distribution throughout the body
and is most numerous in the skin
 mucous membranes, deep fascia, muscles,
and visceral organs
 The distal arborizations are located in the
epithelium between the cells, the
epithelium of the skin, the cornea, and the
mucous membranes lining the digestive
and urinary tracts, as well as in all the
visceral organs and blood vessels.
 Certain specialized epithelial cells
(neuroepithelium), such as those found in
taste buds, olfactory epithelium, and the
cochlear and vestibular organs (hair cells),
receive free (receptor) endings.
 Tendons, joint capsules, periosteum, and
deep fascia
 Pain, touch, pressure, and tension, and
respond indirectly through so-called
neuroepithelia to sound, smell, taste, and
position sense.
 May be myelinated or unmyelinated
 Merkel’s corpuscles are slowly adapting
type I mechanoreceptors that are
distributed in the germinal layer (stratum
basale) of the epidermis.
 Groups of 5 or 10 are interspersed among
the basal layer cells.
 Unmyelinated free nerve endings form an
axonal expansion (e.g., Merkel’s disk) that
is closely applied to a modified epidermal
cell (Markel’s cell).
 Merkel’s cells are found in glabrous skin in
outer sheaths of the hairs in hairy skin.
 Found in areas of transition between hairy
skin and mucous membrane.
 Synapse like junctions have been observed
between Merkel’s disks and Merkel’s cells;
their functional significance is uncertain.
 Receptor subserves the sensory modality of
constant touch or pressure and is
responsible for the tactile gnosis of static
objects.
 Important for Braille reading
 The discharge frequency of Merkel’s
corpuscles is temperature-dependent.
 Cooling the skin increase the discharge
frequency, and warming inhibits the
discharge rate.
o ENCAPSULATED NERVE ENDNGS
 This group of receptors include the
corpuscles of Meissner, Vater-Pacini, Golgi-
Mazzoni, and Ruffini
 The so-called end bulbs
 The neuromuscular spindles; and the
tendon organ of Golgi
o MEISSNER’S TACTILE CORPUSCLES
 Meissner’s corpuscles are elongated,
rounded bodies of spirals of receptor
endings that are fitted into dermal
papillae beneath the epidermis they are
about 100 um in diameter.
 A Meissner’s corpuscle possesses a
connective tissue sheath that encloses the
spiral stacks of horizontally arranged
epithelioid cells.
 The endoneurium is continuous with the
capsule.
 When the myelin sheath terminates, the
axon (A beta fiber) arborizes among the
epithelial cells.
 For one to four myelinated axons, as well
as unmyelinated axons, enter the capsule.
 Meissner’s corpuscles are distributed
widely in the skin but are found in the
greatest numbers in the hairless
(glabrous) skin f the finger, palm of the
hand, plantar surface of the foot, toes,
nipples, and lips.
 Rapidly adapting mechanoreceptors
 Sensory modality subserved by Meissner’s
corpuscles is low-frequency (30 to 40 Hz)
flutter-vibration and moving touch.
 Under sustained pressure, and impulse is
produced at the onset, removal, or change
of magnitude of the stimulus.
 Meissner’s corpuscles are thus best suited
to signal direction and velocity of moving
objects on the skin.
o VATER-PACINI CORPUSCLES
 Vater-Pacini , more commonly known as
Pacinian, corpuscles are the largest and
most widely distributed encapsulated
receptor organs.

 Range up to 4 mm in length but usually
are smaller, they are the only macroscopic
receptor organ in the body.
 The capsule is elliptical in shape and is
composed of concentric lamellae of
flattened cells (fibroblasts) supported by
collagenous tissue that invests the
unmyelinated distal segment of a large
myelinated (A beta) axon.
 The interlamellar spaces are filled with
fluid.
 Provided with their own blood supply,
which also makes them unique.
 Histologically, when cut or sectioned, they
look like a divided onion to which they
have been likened.
 Vater-Pacini corpuscles are
mechanoreceptors that are sensitive to
vibration.
 Maximally responsive at 250 to 300 Hz
 Corpuscles are rapidly adapting receptors
that respond only transiently to on
vibration and off vibration or at the end
of a step-wise change in stimulus
position.
 The recovery cycle of this receptor is very
short (5 to 6 ms)
 Rapid adaptation of Pacinian corpuscles is
a function of the connective tissue capsule
that surrounds the central neural
elements.
 The removal of the connective tissue
capsule transforms a Pacinian corpuscle
from a rapidly adapting receptor to a
slowly adapting one.
 Distributed profusely in the subcutaneous
connective tissue of the hands and feet.
 Found in the eternal genitalia, nipples,
mammary glands, pancreas and other
viscera, mesenteries, linings of the pleural
and abdominal cavities, wall of the blood
vessels, periosteum, ligaments, joint
capsules, and muscles.
 Of the estimated 2 x 19 Pacinian
corpuscles in he human skin, more than
one-third are in the digits of the hand and
more than 1000 can be found in a single
finger.
o GOLGI-MAZZONI CORPUSCLES
 Golgi-Mazzoni corpuscles are quickly
adapting receptor organs that are
lamellated (like the Pacinian corpuscles)
 Distributed in the subcutaneous tissue of
the hands, on the surface of the tendons,
in the periosteum adjacent to joints, and
elsewhere.
 Detection of vibration with a maximal
response under 200 Hz
o RUFFINI’S CORPUSCLES
 Elongated and complex
 Found in the dermis of the skin, especially
the fingertips, but are widely distributed,
especially in joint capsules
 Receptor endings within the capsule ramify
extensively among the supporting
connective tissue bundles
 Type II slowly adapting mechanoreceptors
have been associated with sensations of
pressure and touch as a velocity and
position detector
 Discharge of Ruffini’s corpuscles is
temperature-dependent increasing with
skin cooling and decreasing with skin
warming.
 Three types of Ruffini’s corpuscles have
been identified in joint capsules, based on
their position-related discharge.
 All three maintain constant baseline
output, but each type responds
differently.
 One type responds maximally at extreme
flexion, another type at extreme
extension, and a third midway between
flexion and extension of the joint.
o END BULBS
 The end bulbs resemble the corpuscles of
Golgi-Mazzoni
 Have a connective tissue capsule enclosing
a gelatinous core in which terminal,
unmyelinated endings arborize extensively.

 The end bulbs of Krause have been

associated with sensations of temperature
(cold) and are located strategically and
distributed widely.

 The structural complexity of these end

bubs varies remarkably, as does their size.

BRAINSTEM SYNDROME
FIG.4.69. SYNDROME of the RED NUCLEUS
(BENEDICT SYNDROME)

 Medial lemniscus:
contralateral impairment of
touch, position, and vibration
sense
 Red nucleus: contralteral
hyperkinesia (chorea,
athetosis)
 Substantia nigra:
contralateral akinesia
(parkinsonism)
 Root fibers of the oculomotor
n.: ipislateral oculomotor palsy
with fixed and dilated pupil.

Impairment of
Touch, postiion
and vibration sense

Hyperkinesia

r.n. = red nucleus

p. th. = spimothalamic tract
m.l. = medial lemniscus
Py = pyramidal tract

Fig.4.70. SYNDROME of the CEREBRAL PEDUNCLE
(WEBER SYNDROME)
 Substantia nigra: akinesia
(parkinsonism)
 Corticospinal fibers:
contralateral spastic
hemiplegia
 Corticonuclear fibers:
contralteral supranuclear
facial and hypoglossal nerve
palsies
 Corticopontine tract:
contralteral dystaxia
 Root fibers of the
occulomotor n.: ipsilateral
oculomotor palsy with fixed
and dilated pupil
Supranuclear oculo-
Facial and motor nerve
Hypoglossal palsy
Nerve palsies
Spastic paralysis
Rigidity,
Parkinsonism,
rest tremor
Fig. 4.60. DORSOLATERAL MEDULLARY
SYNDROME
(WALLENBERG SYNDROME)
 Inferior vestibular nucleus: nystagmus and tendency to
fall to ipsilateral side
 Dorsal nucleus of the vagus n.: tachycardia and
dyspnea
 Inferior cerebellar peduncle: ipsilateral ataxia and
asynergia
 Nucleus of the tractus: ageusta
 Nucleus ambiguus: ipsilateral paresis of palate, larynx
and pharynx; hoarseness
 Nucleus of the chochlear n.: hearing loss
 Nucleus of the spinal tract of the trigmental n.:
ipsilateral analgesia and the manesthesia of the face:
absent corneal reflex
 Central sympathetic pathway: homer’s syndrome,
hypohidrosis, ipsilateral facial vasodilatation
 Anterior spinothalamic tract: analgesia and
thermanesthesia of the contralateral hermibody
 Central tegmental tract: palata and pharyngeal
myorhythmia
 Reticular formation (respiratory center): singultis
(hiccups)
 Homer’s syndrome, rystagmus,
dysarthria, dysphagia
 Analgesia and thermanesthesia
 Ataxia and asynergia
Fig.4.64. SYNDROME of the
CAUDAL BASIS PONTIS
(MILLARD-GUBLER SYNDROME)
  Medial lemniscus:
contralateral impairment of
touch, position, and vibration Nonspastic paralysis
sense
 Lateral lemniscus: hearing loss
 Nucleus of the facial n.:
ipsilateral peripheral facial
nerve palsy
 Lateral spinothalamic tract: Impairment of touch,
analgesia and thermanesthesia Position, and vibration sense
of contralteral hemibody
 Pyramidal tract: contralteral
spastic hemiplegia
 Abducens n.: ipsilateral
peripheral abducens nerve
palsy.

Spastic paralysis

Flaccid paralysis

Impairment of touch,
Position, and vibration sense

Analgesia and
Thermanesthesia

Medial medullary syndrome (Dejerine Syndrome).

Cause: occlusion at paramedian branches of the vertebral or
basilar artery, often bilaterally.
Cilincal features: ipsilateral flaccid hypoglossal nerve palsy,
contralateral hemiplegia (not spastic) with babinski’s sign,
contralateral posterior column hypesthesia (I.e.., hypesthesia
to touch and pressure, with impaired position sense), and
mystagmus (in case the medial longitudinal fasciculus is
involved by the lesion).

Medial longitudinal fasciculus: nystagmus

Medial lemniscus: contralateral impairment of touch,
vibration, and position sense

Olive: ipsilateral palatal and pharyngeal myorhythmia

Hypoglossal n.: ipsilateral hypoglossal palsy with
hemiatrophy of the tongue
Pyramidal tract: contralateral hemiplegia without spasticity
but with present Babinski reflex.

Hypoglossal palsy