Pathophysiology of nervous system I:
Control of motor function and its disorders – part 1
Organization of nervous system
Neurons, synapses, neurotransmitters
Proprioception and spinal reflexes
Hierarchy of the motoric control systems
Palsy/paralysis – distinction between upper and lower motoneuron disease
Anatomy and physiology of nervous system (NS)
• central nervous system
• spinal cord
• receives and processes sensory information from skin, joints,
and muscles (dorsal horns)
• passes motor commands on to the muscles (ventral horns)
• brain
• brainstem (hindbrain)
• medulla oblongata
• digestion, breathing, heart-beat
• pons
• passes information about movements from the
cerebrum and the cerebellum
• midbrain
• controls many sensory and motor functions, e.g. eye
movements, and the coordination of visual and acoustic
reflexes
• reticular formation
• runs along the whole brainstem, and contains the
summary of all incoming information
• cerebellum
• controls force and movements, and is involved in motor learning
• forebrain
• diencephalon
• thalamus - processing most incoming (sensory)
information, on its way to the cerebrum
• hypothalamus - regulates the autonomous system,
controls the glands
• cerebral hemispheres (telencephalon)
• peripheral nervous system
Functions of NS
• regulation of body homeostasis and functions
• together with endocrine and immune system
• communication with environment
• mental activity
• direct regulation of the
• skeletal muscles (somatic NS)
• myocardium (autonomous NS)
• smooth muscles of vascular and visceral systems
(autonomous NS)
• glands (autonomous NS)
• cells of nervous system
• neurons – excitability, conductivity, synthesis and release
of neurotransmitters
• axons and dendrites
• excitability (action potential)
• myelin sheath
• synthesis and release of neurotransmitters
• synapses
• receiving and transmitting of information
• supporting cells – metabolic support, protection (bloodbrain
barrier), conduction (myelin)
• glia (astrocytes, oligodendroglia, microglia, ependymal cells)
• Schwann cells
Cell of NS - neuron as a functional unit
• large variability of neurons reflecting
their specificity, seize and type
• single α-motoneuron in anterior horns of
spinal cord in thoracic region can have a
length of axon more than a 1 m and it
innervates several hundred to thousands of
muscle fibrils (forming a so called motor
unit)
• other neurons can have a length of less than
a 100 μm and they terminate on bodies of
neighboring neurons
Neurons/action potential/nerve transmission
Synapses/neurotransmitters
• electrical synapses
• chemical synapses
• excitatory – induce depolarisation
• inhibitory – induce hyperpolarisation ( K+ or Cl- permeability)
• messenger molecules
• neurotransmitters – synthesis, storage and release
• AA – Ach, glutamate, glycine, GABA
• peptides – substance P, endorphins
• monoamines (1 NH2) – serotonine, dopamine, norepinephrine, epinephrine
• neuromodulators
• endocanabinoids, substance P, endorphins
• nerve growth factors
• removal of neurotransmitters
• enzymatic degradation (e.g. Ach)
• re-uptake by pre-synaptic neurons (e.g. catecholamines)
• diffusion away
Axonal transport • disorders
• acute
• toxic disruption
• traumatic axonal injury as apart of
traumatic brain injury
• chronic (inherited)
• mutations in motoric proteins,
microtubules etc.
Blood-brain barrier (BBB)
Neural plasticity
• brain’s natural ability to change or adapt
• changes occur in the complex network of neurons that make up
brain
• experiences, thoughts, or memories create new or stronger
connections among neurons
• even in the adult brain, some new neurons are formed and
migrate out into the cortex, taking up the new roles
• at the same time, neural connections and neurons that aren’t
used or are ineffective atrophy and die
Organization of NS and classification of disorders of NS
• afferent system
• disorders of individual senses (sensor organs)
• sensory neuropathies
• pain
• perception of afferent signals and adequate
reactions
• quantitative and qualitative disorders of
conscience
• efferent system
• disorders of somatic motoric (pyramidal)
system
• disorders of extrapyramidal system
• disorders of cerebellum
• disorders of hypothalamus and vegetative NS
• abnormal electric activity of the brain
• epilepsy
• mental abilities
• cognitive disorders
• dementia
• sleep disorders
Aetiology of nervous disorders
• unspecific = disturbances of the
body’s internal environment
• hypoxia
• temperature
• ion concentrations
• substrate/energy availability
• specific for nervous system
• inherited
• genetic
• acquired
• (auto)immune
• ischemia
• hemorrhage
• mechanical injury/trauma
• infection
Motor system a its disorders
Motor system – control and its components
• locomotion + postural adjustments + periodical
movement = motor activity
• motor action is typically a response to sensory
perceptions
• such as fight or flight, searching for shelter in rain,
jerking away from painful object …
• but also – typically in humans – as consequence
of cognition, memory, emotional state and
creativity
• such as smile, writing, dance, playing musical
instrument, painting, sculpting, …
• necessary components of proper motor control
• volition, purpose, plan
• coordination of signals to many muscle groups
• proprioception and postural adjustments
• sensory feed-back
• unconscious processing
• adaptability to changing conditions
• i.e. growth, gain of weight (i.e. shift of center of mass),
immobility of limb etc.
Excellence of human movement and motor functions
• the ease with which we make most of our movements
point to enormous sophistication and complexity of the
motor system
• we have spent decades trying to make machines to perform
simple tasks and human-like robots are nowhere near
Functional Segregation and Hierarchical Organization
• (1) Functional Segregation
• motor system is divided into a number of
different areas throughout the nervous
system that control different aspects of
movement (a “divide and conquer” strategy)
• to understand the functional roles played by each
area is necessary for understanding various
motor disorders
• (2) Hierarchical Organization
• higher-order areas can concern themselves
with more global tasks regarding action, such
as deciding when to act, devising an
appropriate sequence of actions, and
coordinating the activity of many limbs
• they do not have to concern the activity of
individual muscles, or coordinate movements
with changes in posture
• these low-level tasks are performed by the lower
levels of the hierarchy
Hierarchical organisation of the motoric system
• 4 levels:
• (1) the spinal cord
• (2) the brain stem
• (3) the motor cortex
• (4) the association cortex
• It also contains two side loops,
which interact with the hierarchy
through connections with the
thalamus :
• (5) the basal ganglia
• (6) the cerebellum
Level (1) spinal cord: α-motoneurons
• lower alpha-motoneurons (LMNs)
• brainstem – for cranial muscles
• spinal cord (ventral horns) – for neck, torso and limb muscles
• they release acetylcholine on neuromuscular junction and thus allow for muscle contraction
• isometric
• isotonic
• α-motoneurons are absolutely essential for ability to make a movement = the only communication
with muscles
• here all the signals for other systems and levels become integrated
• numerous inputs converge on α-motor neurons = final common pathway
• dendrites are connecting them with many other neurons – important for precision and adequacy of
the movement
• motor neuron pools (or motor nuclei)
• all of the motor neurons in a motor neuron pool innervate a single muscle
• motor unit
• the combination of an individual motor neuron and all of the extrafusal muscle fibers that it innervates
• each individual muscle fiber in a muscle is innervated by one motor neuron, a single motor neuron, however, can
innervate many muscle fibers
• the number of fibers innervated by a motor unit is called its innervation ratio
• low (10-100) in muscles dedicated to delicate movements
• e.g. digits of hands, facial mimic
• high (≥1000) in muscles dedicated to gross movements
• e.g. thigh
• α-motoneurons control muscle force – see next slide
Motoneurons – a size principle – and types of muscle
fibres govern the intensity of the muscle contraction
• size of
motoneurons (=
area of cell
membrane) and
the membrane
potential
• three types of
muscle fibres with
various electrical
and metabolic
properties a thus
various
„fatigability“
Motoneurons – a size principle – and types of muscle
fibres govern the intensity of the muscle contraction
Organization of moto neurons in the spinal cord (anterior horns)
• the flexor-extensor rule
• motor neurons that
innervate flexor muscles are
located posteriorly to motor
neurons that innervate
extensor muscles
• and the proximal-distal rule
• motor neurons that
innervate distal muscles
(e.g., hand muscles) are
located lateral to motor
neurons that innervate
proximal muscles (e.g., trunk
muscles)
Level (1) spinal cord : Muscle Receptors and Proprioception
• Proprioception is the sense of the body’s position in space
based on specialized receptors that reside in the (A) muscles
and (B) tendons
• (A) Muscle spindles signal the length and the rate of change of
length (velocity) of the muscle
• collections of 6-8 specialized muscle fibers that are located within the
muscle mass itself
• they are formed by intrafusal fibers not participating in the active
contraction (unlike extrafusal ones)
• spindles are formed by different types of fibres
• see figure
• these fibres provide different information
(length vs. velocity of its change) – via various
afferents (Ia vs. II)
• each muscle contains many muscle spindles
• muscles that are necessary for fine movements
contain more spindles than muscles that are used
for posture or coarse movements
• intrafusal fibres can contract though – innervation by -motoneurons
• (B) Golgi Tendon Organ located between the muscle and the
tendon signals information about the load or force being applied to
the muscle = inverse stretch reflex
• collagen capsule
• afferents called group Ib fibers weave in between the collagen fibers being
‘crushed’ by movement and thus depolarized
In summary
• Muscle spindles signal
information about the
length and velocity of a
length change of the muscle
• the properties of the various
dynamic and static
responses of muscle spindle
afferents are related to
physiological tremor
• Golgi tendon organs signal
information about the load
or force applied to a muscle
Level (1) spinal cord: spinal reflexes
• reflex is a basic functional unit of motor system
• morphologically they rely on specialized neuronal
circuits controlling the muscle function so that it can
give rise to effective movements
• without the spinal reflexes not even a simple
movement would be possible
• reflex arch
• 1) sensor (e.g. muscle spindle or Golgi tendon organ)
• 2) afferent pathway
• neurons of spinal ganglia entering the spinal cord via the
dorsal roots
• they split into two collaterals:
• to the same spinal segment (monosynaptic)
• afferents to other hierarchies
• 3) centrum of the reflex
• 4) efferent pathway – spinal motoneuron innervating
the muscle
• 5) effector – particular skeletal muscle(s)
• types of reflexes
• monosynaptic
• polysynaptic
Level (1) spinal cord: spinal reflexes
• types of reflexes
• monosynaptic
• stretch or myotatic (e.g. patellar – knee jerk reflex) –
sensor is the muscle spindle
• polysynaptic – interneurons are interposed
between the afferent and efferent neurons (often
defensive)
• flexor (withdrawal reflex) reflex – sensor is the
nociceptor
• activation of a-motoneuron of the particular flexor
• inhibition of a-motoneuron of adjacent extensor
(antagonist)
• crossed extensor response reflex – follows the flexor
one when stimulus is more intense
• extension of the contralateral limb
• the meaning is to better distribute the weight and to
keep balance
• evolutionary probably an old mechanism (now a
rudiment) for optimizing a quadruped stance
Level (1) spinal cord: role of interneurons
• interneurons constitute the majority of spinal neurons
• necessary for complex locomotor behaviors
• left–right coordination to achieve optimal gaits
• walking / running in humans
• in other species walking / trotting / galloping, swimming, flying etc.
• flexor–extensor alternations
• rhythm-generating and pattern-forming spinal circuits
• the four ventromedial descending pathways originating in the brain stem (see Level 2)
terminate among the spinal interneurons controlling proximal and axial muscles
• they use information about balance, body position, and the visual environment to reflexively maintain
balance and body posture
Level (2) brainstem: Descending Motor Pathways
• Role of Descending Pathways on Spinal Circuits
• Voluntary movement and some sensory-driven reflex
actions are controlled by the descending pathways in
order to be appropriate and effective
• Reflex modulation - another critical function is to
modulate/adapt the reflex circuits in the spinal cord
• gamma motoneuron bias
• Desc. motor pathways are organized into two major groups
• Lateral pathways control both proximal and distal muscles
and are responsible for most voluntary movements of arms
and legs
• They include the
• lateral corticospinal tract
• rubrospinal tract
• Ventro-medial pathways control axial muscles and are responsible for
posture, balance, and coarse motor control of axial and proximal
muscles
• They include the
• vestibulospinal tracts (both lateral and medial) – positioning of the head
• reticulospinal tracts (both pontine and medullary) – adaptation of movements
to level of alertness and emotions
• tectospinal tract – space orientation and auditory signal adjustment
• anterior corticospinal tract
• Parallel and Serial Processing
• the flow of information through the motor system has both a serial
organization (communication between levels) and a parallel organization
(multiple pathways between each level)
• this is critically important in understanding the various dysfunctions that
can result from damage to the motor system
• it allows to at least partly compensate for damage at certain parts of the
control (e.g. corticospinal tract) and to recover voluntary motoric to
some extent*sub-cortical (brain stem) tracts
Overview of tracts in a spinal cord
Medial and lateral descending brain stem pathways
involved in motor control
• The rubrospinal tract
• terminates primarily in the cervical and thoracic portions of the spinal cord,
suggesting that it functions in upper limb but not in lower limb proximal muscle
control
• decerebration
• a complete transection of the brain stem interrupting all input from the cortex
(CTS) and red nucleus (via rubrospinal tract) to distal muscles of the extremities
• the rubrospinal tract excites flexor motor neurons and inhibits extensor motor neurons
• leads to hyperactivity in extensor muscles in all four extremities which
is called decerebrate rigidity together
with coma, fixed and dilated pupils,
absent eye movements and a Cheyne–
Stokes respiratory pattern
• causes: uncal herniation due to large
tumours, haemorrhages, strokes
or abscesses
• decortication
• the rubrospinal tract excites flexor
motoneurons and inhibits extensor
motoneurons
Corticospinal/corticobulbar tract
• The corticospinal system controls motor neurons and interneurons in the
spinal cord
• The corticobulbar system controls brainstem nuclei that innervate cranial
muscles
• trigeminal, facial, and hypoglossal nuclei
• not strictly contralateral manifestation
• CST originates in the motor cortex
• the majority of CST axons originate from pyramidal cells located in the inferior
part of cortical layer V in the primary motor (M1)
• travels via capsula interna, crus cerebri (midbrain), pyramids of medulla oblongata
– decussation (here it splits into two funiculi)
• CST has approximately 1 million nerve fibres with an average conduction velocity
of approximately 60m/s using glutamate as their transmitter substance
• the primary pathway that carries the motor commands that underlie
voluntary movement in humans
• the lateral corticospinal tract (90% of axons) is responsible for the control of the
distal musculature
• a particularly important function of the LCST is the fine control of the digits of the hand
• the anterior/ventral corticospinal tract (10% of axons) is responsible for the
control of the axial (trunk) and proximal musculature
• both the lateral and anterior corticospinal tracts are crossed pathways;
they cross the midline at different locations, however
• dominance of CST in humans reflects evolutionary pressure on increasing
dexterity and skilled expression of higher brain functions
Note the principle of contralateral organisation of
pathways is always preserved!!!
CST onto- and fylogenesis
• Humans neonatal brain being moderately myelinated and
only 25% of its adult size
• CST axons reach the lower part of the cervical spinal cord by 24
weeks post-conception, and grey matter innervation begins a
few weeks later
• The relative importance of CST to voluntary movement
greatly varies across the species
• humans > primates >> other mammalian vertebrates
• non-mammalian vertebrates have essentially no CST
• The percentage of axons in CST that innervate a-motor
neurons directly is greater in humans and nonhuman
primates than in other mammals
• presumably reflecting the increased manual dexterity of
primates
• in other species most of the CST connects with spinal
interneurons
• therefore, damage to the CST results in a permanent loss
of the fine control of the extremities most markedly in
humans
• while nearly undetectable in other mammals (e.g. cats or dogs)
Organization of the motor system in vertebrates and man
• In most vertebrates, including nonhuman
primates, the extrapyramidal and
pyramidal fiber systems run in parallel
from the motor cortices (MC) to the
motoneuron pools of the brainstem and
spinal cord.
• The extrapyramidal system consists of a
series of cortical projections interrupted at
the basal ganglia (BG) and brainstem
tegmentum (TEG) whence tegmentospinal
projections originate (chiefly,
reticulospinal, vestibulospinal, tectospinal
and rubrospinal tracts).
• Right. The adoption of obligate erect
bipedalism in humans was paralleled by a
profound cerebral reorganization. These
changes are reflected in an unprecedented
increase in the ansa lenticularis fiber
system. The ansa directs the projections
from widespread cortical areas into the
thalamic motor nuclei (mt), which project
back to the motor cortices that give rise to
the pyramidal tracts. The increase in the
pyramidal tracts (MP), in turn, is paralleled
by an unprecedented decrease of the
descending motor (extrapyramidal)
pathways. Note the perpendicular and
parallel orientations of the quadrupedal
and human body axes (arrows),
respectively, in relation to gravity (g). mp:
medullary pyramids.
Level (3): Motor cortex
• comprises three different areas of the
frontal lobe
• the primary motor cortex (Brodmann’s area 4)
• function: regulation of the onset, force, direction,
extent and the speed of the movement (=
regulation of the execution of movements rather
than control of individual muscles)
• the premotor cortex
• function: more complex, task-related processing,
selection of appropriate motor plans for voluntary
movements (often based on visual stimuli or on
abstract associations)
• the supplementary motor area
• function: programming complex sequences of
movements and coordinating bilateral movements
(based on remembered sequences of movements)
• electrical stimulation of these areas elicits
movements of particular body parts
• though different for each of the 3 areas
• they are somatotopically organized
• motor cortex “homunculus”
Cyto-architecture of the motor cortex
• brain cortex is very sensitive to
hypoxia
• motor cortex even more
• pre-/peri-/ and early post-natal
development are vulnerable periods
Cortical Afferents and Efferents and cytoarchitecture
• efferent pathways
• directly to alpha motor neurons via the corticospinal
tract
• the corticorubral tract to modulate the rubrospinal tract
• the corticotectal tract to modulate the tectospinal tract
• the corticoreticular tract to modulate the reticulospinal
tracts
• the corticostriate tract to the caudate nucleus and
putamen of the basal ganglia
• the corticopontine tract and cortico-olivary tract to the
cerebellum
• the corticocortical pathways to other brain areas (bi-
directional)
• afferent pathways
• the corticocortical pathways from other brain areas (bi-
directional)
• indirectly via the corticothalamic pathways (from the
cerebellum and basal ganglia)
Level (4): Association cortex
• the prefrontal cortex
• the posterior parietal cortex
• disorders
• apraxia
• agnosia
• aphasia
Levels (1-6): Control of voluntary movement
• Commands for voluntary movement originate in cortical association areas
• The cortex, basal ganglia, and cerebellum work cooperatively to plan movements
• Movement executed by the cortex is relayed via the corticospinal tracts and corticobulbar tracts to spinal motor
neurons
• The cerebellum provides feedback to adjust and smooth movement
Disorders of muscle tone and movement
• paralysis (UMND or LMND)
• incl. spasticity or flaccidity
• basal ganglia and cerebellum disorders (i.e.
extrapyramidal system)
• incl. rigidity and abnormal movements
• abnormal electric activity of the brain
• epilepsy
• disorders of neuromuscular junction
• skeletal muscle disorders
• muscle atrophy
• muscle dystrophy
Palsy / paralysis
Upper and Lower moto neuron disease
Paralysis ( voluntary muscle activity and weakness)
• loss of muscle function / weakness in part of your body due to UMND or LMND (= loss of the
ability to move some or all of the body)
• degree/terminology
• partial (some motor units) = paresis
• complete (whole muscle) = plegia
• can be accompanied by a loss of feeling (sensory loss) in the affected area if there is sensory
damage as well as motor
• i.e. depending on aetiology
• paralysis always involves weakness And changes of muscle tone, which is different in UMN vs.
LMN injury
• spastic paralysis – lesion of UMNs (i.e. central) in the primary motor cortex, internal capsule, corticospinal
and bulbar tracts)
•  muscle tone (spasticity)
• loss of the control/inhibition of spinal stretch reflexes and gamma motoneurons
• a velocity-dependent increase in muscle tone that manifests with resistance to movement
• a clasp knife phenomenon
• must be distinguished from rigidity! – extrapyramidal sign (a cog wheel phenomenon)
•  spinal reflexes (hyperreflexia) or even clonus
•  pathologic reflexes (= a deliberation phenomena) such as Babinski
• flaccid paralysis – lesion of LMNs (i.e. peripheral) in the ventral spinal horns and ganglia of head nerves in
brainstem)
•  muscle tone (hypotonia)
•  muscle mass (atrophy): muscle fibers deprived of necessary trophic factors
• fasciculations: damaged LMN can produce spontaneous action potentials and muscle twitch
• fibrillations with further degeneration of LMN – individual muscle fibres twitch
•  or no spinal reflexes (hypofreflexia)
Etiology of paralysis
• UMND – spastic paralysis
• generalised lesions of UMNs
• amyotrophic lateral sclerosis
• focal lesions of UMNs
• ischemia
• stroke
• cerebral palsy
• haemorrhage (stroke)
• epidural or subdural
• injury (head and spine)
• central demyelinisation
• multiple sclerosis
• neuroinfection
• brain tumours
• LMN – flaccid paralysis
• spinal and peripheral nerve injury
• ventral root lesions
• hernia of the intervertebral disc, tumor, vertebral
fracture, osteophyt, compression
• spinal muscular atrophy
• peripheral demyelinisation
• Guillain Barre
• infection
• poliomyelitis (infantile paralysis)
Selected examples of paralyses
due to UMND or LMND
Example (1) - UMND: Stroke
Example (1) - UMND: Stroke
• presentation of stroke syndrome depends on the
side of the hemisphere affected!!!
• see the motor homunculus to correlate with artery
supply
• ACA infarction / stroke
• motor deficits characteristically involving the lower
extremity contralateral to the infarct site
• MCA infarction / stroke
• the most common type (2/3 of cases) of cerebral
vascular infarcts
• MCA supplies the largest brain territory, infarcts are
associated with many types of neurological deficits
• MCA comprises
• corticospinal tract, which is responsible for fine motor
activity of the hands, a
• corticoreticulospinal tract, which is involved in postural
control and locomotor function, and therefore, motor
weakness is one of the most disabling sequelae of a middle
• posterior circulation
Example (2) - UMND: Spinal cord injury (SCI)
• leading causes are vehicle accidents,
violence, and sports injuries
• the mean age of patients is 33 years old
• men outnumber women with a nearly 4:1 ratio
• approx. 52% of SCI cases result in
quadriplegia and about 42% lead to
paraplegia
• immediately after the injury there is a
spinal shock (approx. 2 weeks)
• depression of all the functions
• subsequently reflex responses return and
become hyperactive (knee jerk or withdrawal
reflexes)
• below the lesion SCI affects
• motor functions
• spinal reflexes
• afferent sensation
• vegetative functions
Example (2) - UMND: Spinal cord injury (SCI)
• (A) complete transversal lesion
• immediately after injury – spinal shock
• no muscle tension, no reflexes, no perception, blood pressure
instability (neurogenic shock), loss of thermoregulation, loss of
function over the rectum, urinary bladder and bowels
• later spastic paralysis, hyperreflexia, loss of perception
• C1 - C4 – acute respiratory failure
• below C5 + upper Th
• quadriplegia
• loss of sensation
• spontaneous ventilation (intact innervation of diaphragm)
• complete loss of vegetative sympathetic function (hypotension)
• loss of caudal parasympathetic function (defecation and urination
reflexes)
• lower Th, L and S
• paraplegia
• loss of sensation
• loss of caudal parasympathetic function (defecation and urination
reflexes)
• normal ovary cycle and pregnancy possible (no pain during the
labour though)
• erection and ejaculation possible after tactile stimulation
• (B) lateral spinal hemisection (Brown-Sequard syndrome)
• paralysis and loss of proprioception on the site of lesion
• loss of pain and thermoreception on the contralateral site
Current and future management of SCI
• SCI represents a great therapeutic
management challenge
• a negative nitrogen balance due to
immobilization
• body weight compresses the circulation
causing decubitus ulcers to form
• healing is poorly and prone to infection because
of body protein depletion
• Ca2+ is released in large amounts from skeleton
and tissues leading to hypercalcemia,
hypercalciuria, and formation of calcium stones in
the urinary tract
• combination of stones and bladder paralysis
cause urinary stasis, which predisposes to urinary
tract infection, the most common complication of
SCI
• spinal cord regeneration?
• administration of neurotrophins shows some
promise in experimental animals
• embryonic stem cells at the site of injury
• electronic devices mimicking stimulation by UMN
Example (3) - UMND: Cerebral palsy (CP)
• non-progressive neurological disorders that occur due to the exposure of
the (developing) brain to hypoxia
• before or during childbirth (70–80% of cases)
• toxins, infections
• pre-term deliveries
• perinatal asphyxia
• during early childhood
• up to 3yrs of age
• adulthood
• cardiac arrest
• hemorrhage
• stroke
• symptoms of CP
• motor symptoms
• spasticity, ataxia, deficits in fine motor control, and abnormal gait (crouched or “scissored gait”)
• sensory deficits
• loss of vision and hearing as well as learning difficulties and seizures
• CP subtypes
• spastic CP – classical UMND, typical and most prevalent
• spasticity, hyperreflexia, clonus, and a positive Babinski sign
• dyskinetic CP - due to damage of extrapyramidal motor areas (see further)
• abnormal involuntary movements (chorea and athetosis)
• mixed CP
• hypotonic CP
• truncal and extremity hypotonia, hyperreflexia, and persistent primitive reflexes
Example (4) - UMND: Demyelinisation - multiple sclerosis
• young adults (20 – 45), 2x more women, moderate regions of the
Northern hemisphere
• etiology
• genetic predisposition (MHC genes)
• environmental triggers
• infection, vitamin D, …
• pathogenesis
• myelin produced by oligodendrocytes permits rapid conductance
• loss of myelin results in conduction abnormalities (decreased velocity to
block)
• impaired BBB allows immune cells to enter the CNS
• autoimmune injury (auto-agressive T-cell and macrophage mediated) of the
oligodendrocytes (ODCs)
• active destruction of ODCs and myelin results in the formation of sharpedged
demyelinated patches in CNS - plaques
• initial inflammation follows in the formation of the scar (sclerosis)
Example (4) - UMND: Demyelinisation - multiple sclerosis
• symptoms
• predilection for optic nerve (vision impairment), periventricular white matter, brain stem
(swallowing and speech), cerebellum (gait and coordination), corticospinal tract (muscle
strength), spinothalamic tract (vibration sensation)
• psychological manifestation (fatigue, mood swings, depression, euphoria, loss of memory)
reflects involvement of the white matter of the cerebral cortex
• periodical exacerbations and remission with subsequently less complete restoration of the
neural function
• disease course
• relapsing-remitting (85%)
• secondary progressive
• primary progressive
• Guillain-Barre syndrome
• post-inflammation peripheral polyneuropathy due to demyelinisation (Schwan cells)
Example (5) - LMND: Polio and the beauty of vaccination
Example (6) – L+UMND: Amyotrophic Lateral Sclerosis
• synonym Lou Gehring disease
• fatal and incurable neurodegenerative disorder arising from a progressive loss of
motoneurons in the spinal cord, brainstem and motor cortex
• 1) LMNs of the ventral spinal horns
• 2) motor nuclei of the brain stem
• esp. n. hypoglossus
• 3) UMNs of the motor cortex
• sensory, vegetative and some motor neurons (occulomotory) as well as intellect
capacities are spared
• symptoms
• early symptoms of ALS often include increasing muscle weakness, especially involving the arms
and legs, speech, swallowing or breathing
• later on, increasing impairment of moving, swallowing (dysphagia), and speaking or forming
words (dysarthria)
• muscle weakening and paralysis irrevocably lead to cell death with 3-5 years following the
appearance of the first symptoms
• onset typically between the ages of 40 and 70, more common in men than in women
• etiology
• ~90% of ALS cases are sporadic
• apparently at random with no clearly associated risk factors, negative family history of the disease
• ~10% are familial
• >100 distinct mutations in the ubiquitously expressed enzyme Cu/Zn superoxide dismutase (SOD1, chrom.
21) have been identified in approximately 20% of familial cases of ALS
• pathogenesis – just hypotheses
• ROS toxicity – damage of axonal transport ?
• exotoxicity – activation of glutamate-gated channels ?
• autoimmunity ?