NEURO

LO 2 WEEK 5

LESION IN SPINAL CORD AND PERIPHERAL NERVES

LESIONS OF CENTRAL MOTOR PATHWAY
- PATHOGENIS OF CENTRAL SPASTIC PARESIS
o Fase akut lesi corticospinal tract -> deep tendon reflex are hypoactive & flaccid weakness of the
muscle
o Reflexes bakal balik few days & weeks later -> jadi hyperactive -> karena muscle spindles respond
more sensitively to stretch than normal, particularly in the upper limb flexors and the lower limb
extensor.
o Hypersensitivity -> due to a loss of descending central inhibitory control of the fusimotor cells
(gamma motor neuron) that innervate the muscle spindles,
o Hyperreflexia, Babinski sign, spastic increased tone, diminish muscular strength & impaired fine
motor control
- Localization of Lesions in the Central Motor System
o Lesi at Cerebral Cortex
 Such an tumor, infarct, traumatic injury -> weakness of part of the body on the opposite
side
 Hemiparesis seen in face and hand lebih sering -> krn bagian tubuh ini punya large cortical
representation
 Typical clinical finding:
 Predominantly distal paresis of upper limb
 Weakness is incomplete -> paresis bukan plegia
 Flaccid karena nonpyramidal motor pathway are largely spared
 Irritative lesion bisa nyebabin focal seizures
o Lesi at Internal Capsule
 Ex. Hemorrhage or ischemia
 Contralateral spastic hemiplegia -> lesi setinggi ini affect both pyramidal and nonpyramidal
fibers -> karena di level setinggi ini mreka deket bgt
 Corticobulbar biasanya involved juga -> jadi ada facial palsy. Bisa accompanies by central
hypoglossal nerve palsy.
 Ga ada cranial nerve lain yang deficit -> Soalnya mreka masih bilateral innervated
 Contralateral paresis itu awalnya flaccid (shock phase) -> tapi jadi spastic within hours or
days karena bersamaan damage to non-pyramidal fibers.
o Lesi at Level of the Cerebral Peduncle (crus cerebri)
 Vascular process, hemorrhage, tumor
 Produce contralateral spastic hemiparesis -> biasanya ada ipsilateral oculomotor nerve
palsy (weber syndrome)
o Lesi at Pontine Lesions
 Involving pyramidal tract -> tumor, brainstem ischemia, hemorrhage
 Nyebabin contralateral or possibly bilateral hemiparesis
 Sbnernya gak smua fibers dr pyramidal tract involve , karena fibersnya spread over wide
cross sectional area at pontine level.
 Jarang kena facial ama hypoglossal soalnya nucleinya lebih ke dorsal portion sebelum reach
this lesions.
 Biasanya diikutin oleh ipsilateral trigeminal nerve deficit & abducens palsy
o Lesi at Medullary Pyramid
  Usually tumor
 Bisa damage pyramidal tract fibers
 Menyebabkan flaccid contralateral hemiparesis
 Weakness Is less than total -> karena remaining descending pathway are preserved
o Lesi at Pyramidal Tract in the Spinal Cord
 Lesion affecting pyramidal tract AT CERVICAL LEVEL
 Tumor, myelitis, trauma
 Menyebabkan ipsilateral spastic hemiplegia -> ipsilateral karena tract nya udah crossed at
higher level -> terus spastic karena contains nonpyramidal as well as pyramidal fibers at this
level.
 Bilateral lesions in upper cervical spinal cord -> quadriparesis or quadriplegia
 Lesi affect pyramidal tract in the thoracic spinal cord (trauma, myelitis)
 Spastic ipsilateral monoplegia of the lower limb
 Bilateral involvement causes paraplegia

LESION OF PERIPHERAL COMPONENTS OF MOTOR SYSTEM

- Clinical syndromes of Motor Unit Lesions
o Flaccid Paralysis -> disebabkan oleh interupsi motor units at any site, bisa di anterior horn, anterior
roots, nerve plexus, peripheral nerve.
o Affected muscles are extremely weak (plegic), marked diminution of muscle tone (hypotonia), loss
of reflexes.
o Muscle atrophy sets within a few weeks
o Kalo ada paralysis limb atau ada somatosensory atau autonomic deficits -> lesion nya biasanya distal
to nerve roots and located either di nerve plexus atau di peripheral nerve.
- Spinal Cord Syndromes
o Key points
 Spinal cord kan isinya motor, sensory, autonomic fibers & nuclei yang masing2 nya saling
berhubungan -> lesi di spinal cord itu nyebabin wide variety neurological deficits ->
combined each other
 Careful clinical exam harus dilakuin untuk bisa nentuin precise lokalisasi lesi nya dimana
o Spinal Cord Lesions
 Biasanya affect only white matter (posterior column lesions) or only gray matter (acute
poliomyelitis) -> tapi jg bisa affect both
 Syndrome of the Dorsal Root Ganglion
 Infection one or more spinal ganglia by neuro tropic virus
 Paling sering di thoracic region
 Nyebabin painful erythema of corresponding dermatomes -> followed by formation
of variable number of cutaneous vesicle -> Herpes Zoster -> ada unpleasant,
stabbing pain, paresthesia in affected area
 Kalo ada involvement dari anterior horns -> flaccid paresis (tapi jarang)
o Posterior Root Syndrome
 Kalo ada 2 atau lebih adjacent posterior roots yang completely divided -> sensation
corresponding to dermatomes is partially or totally lost
 incomplete posterior root lesions -> affect different sensory modality to variable
extent biasanya ada pain sensation
 lesi nya biasanya interrupts peripheral reflex arc -> sensory deficit ada ditambah
hypotonia, hyporeflex, bahkan areflexia in muscle supplied by the affected roots.

o Posterior Column Syndrome

 Posrterior column biasanya kena itu secondary -> biasanya ada proses patologi yang kenain
dorsal root ganglion cells & posterior roots
 Lesions of posterior column -> impair position and vibration sense, discrimination,
stereognosis
 Positive Romberg sign, gait ataxia yang diperparah kalo matanya tutup (sensory
ataxia)
 Posterior column lesions also
produce hypersensitivity to pain
 Causes: Vit B12 deficiency
(funicular myelosis), AIDS
associated myelopathy, spinal
cord compression (cervical spinal
stenosis), bisa juga tabes dorsalis
due to syphilis tapi jarang
o Posterior Horn Syndrome
 Can be a clinical manifestation of syringomyelia, hematomyelia, some intramedullary
spinal cord tuors.
 Posterior horn lesi -> segmental somatosensory deficit
 Only pain and temperature and pain sensation yang lost -> corresponding ipsilateral
segments -> karena modality nya di kondusi secara centrall melewati second neuron in the
posterior horn.
 Loss of pain and temperature sensation
with sparing of posterior column = called
dissociated somatosensory deficit -> bisa
ada spontaneous pain di analgesic area
 Kalo ada lesi below this level -> misalnya
lateral spinothalamic tract (lying in the
antolateral funiculus). Itu masih intact
pain and temperature sensationnya. Dan masih bisa meneruskan konduksi.
o Gray Matter Syndrome
  Damage to central gray matter of spinal cord caused by syringomelia, hematomyelia,
intramedullary spinal cord tumors, atau apapun yang menganggu fibers pathway yang akan
pass through gray matter,
 Most prominent affected fibers adalah yang originate in posterior horn cells & conduct
coarse pressure -> touch, pain, temperature -> these fibers decussate in central gray matter
& ascend in the anterior and lateral spinothalamic tracts.
 Lesion affecting them bikin bilateral associated sensory deficit in cutaneous area ke area
yang di supply sama damage fibersnya
 Syringomelia
 Characterized oleh pembentukan 1 atau lebih dari 1 cavitas yang isinya fluid di spinal
cord (kalo di brainstem: Namanya syringobulbia)
 Cavities -> called syringes -> bisa terbentuk oleh macam2 mekanisme dan
tergantung distribusi pattern nya masing2.
 Some syringes itu adalah expansi dari central canal of spinal cord -> which may or
may not communicate with fourth ventricle , bisa juga dari lekukan yg keluar dari
parenchyma.
 Hydromelia -> term ini digunakan untuk communicating syringes of central canal,
tapi lebih refer ke idiopathic, congenital variant of syringomyelia dimana syrinx nya
communicates with Subarachnoid space.
 Syringo melia most commonly affect cervical spinal cord -> produce loss of pain and
temperature sensations in the shoulder and upper limbs
 Kalo syrinxnya progressively expand -> syrinx nya bisa ngerusak long tract of spinal
cord -> bikin spastic para paresis & disturb bladder, bowel, and sexual function.
 Syringobulbia -> nyebabin unilateral atrophy of tounge, hypalgesia or analgesia of
the face, various type of nystagmus.

- Funicular Myelosis (kombinasi lesi of posterior columns and corticospinal tracts)

o Biasanya gara2 vitamin B12 deficiency karena lack of gastric intrinsic factor , known in such cases
“subacute combined degeneration”
o Foci of demyelination biasanya di cervical and thoracic region in posterior columns (70-80%), bisa di
pyramidal tract (40-50%), biasanya gray matter gak kena,
o Posterior column damage -> loss of position and vibration sense in lower limbs -> spinal ataxia,
positive Romberg sign
o Accompanying pyramidal tract damage -> spastic paraparesis with hyperreflexia and bilateral
Babinski sign
- Anterior Horn Syndrome
o biasanya acute polio myelitis & spinal muscle
atrophy -> affect anterion horn cells biasanya di
cervical and lumbar enlargement of spinal cord
 o In poliomyelitis (viral infection) -> jumlah anterior horn cells itu secara akut & irreversible lost ->
mainly in lumbar region -> causing flaccid paresis of muscles in the corresponding segments
o Proximal muscle biasanya lebih strongly affected dari pada distal -> musclesnya biasanya atrophy
- Amyotrophic Lateral Sclerosis (combined anterior horn and pyramidal tract syndromes)
o Terjadi karena degeneration of both cortical and
spinal motor neurons
o Clinical picture = combination of flaccid and spastic
paresis
o Bisa juga karena simultaneous damage to UMN
(with consequent pyramidal tract degeneration and
spasticity) -> reflex bisa dan bahkan berlebihan
o Accompanying degeneration of motor cranial nerve
nuclei -> bikin dysarthria and dysphagia (progressive bulbar palsy)
- Syndrome of Corticospinal Tract
o Loss of cortical motor neuron = diikuti oleh
degenerasi dari corticospinal tract in number of
different diseases
 Primary Lateral Sclerosis
 Hereditrary Spastic Spinal Paralysis
o Patient biasanya complains feeling of heaviness,
weakness in lower limb
o Spastic paresis with a spastic gait disturbance
gradually develop and worsens
o Reflexnya lebih tajam dari pada normal
o Spastic paresis of upper limbs does not develop until much later.

- Syndrome of combined involvement of posterior columbs, spinocerebellar tracts, (possibly) pyramidal

tract
o Ketika pathological process affects semua system ini -> DD yang harus di include spinocerebellar
ataxia of Friedreich type, axonal form of a hereditary neuropathy (HSMN II) , and other ataxias.
o Friedreich Ataxia
 Biasanya sebelum umur 20 tahun with loss of dorsal root ganglion cells -> jadi posterior
column degeneration
 Impairment of position sense, two point
discrimination, stereognosis, with spinal
ataxia and postivie Romberg sign
 Pain and temperature sense masih bisa
 Ataxia nya severe karena both posterior
column & spinocerebellar is involved
 Gait nya uncoordinated, become spastic
over time as pyramidal tract progrresively
bakal degenerasi juga.
 About half of patients manifestasi
skeletal deformities -> scoliosis or pes cavus (friedreich foot)
o According to Harding, Friedreich ataxia bisa di diagnosis kalo ad clinical criteria:
 Progressive ataxia of no other known cause, begin before 25 th
 Autosomal rescess inheritance
 Absent deep tendon reflex in lower limb
 Posterior column disturbance
  Dysarthria within five years of onset

SPINAL CORD HEMISECTION SYNDROME (BROWN-SEQUARD SYNDROME)

- Rare, biasanya incomplete -> paling sering gara-gara spinal trauma and cervical disk herniation
- Interruption of descending motor pathway on one side of spinal cord -> initially flaccid, ipsilateral paresis
below elvel of lesions (spinal shock), lama2 jadi spastic & accompanied by hyperreflexia, Babinski,
vasomotor disturbance
- Pada saat yang bersamaan kalo posterior column nya rusak on one side of spinal cord -> bikin ipsilateral loss
of position sense, vibration, and tactile discrimination below the level of the lesions.
- Ataxia yg disebabin sama posterior column yg rusak itu gak keliatan soalnya emg udah ada coexisting
ipsilateral paresis.
- Pain and temperature sensation gak kena on the side of the lesions (ipsilateral), soalnya fibers subserving
modalitas ini udah crossed to the other side to ascend in lateral spinothalamic tract -> tapi pain and
temperature sensation lost contralaterally below the level of lesion -> because the ipsilateral (crossed)
spinothalamic tracts are interrupted.
- Simple tactile sensation gak rusak -> karena modalitas ini di served oleh two different fiber pathway:
posterior column (uncrossed) and anterior spinothalamic tract (crossed)
- Hemi section of coard bikin one of these pathway masih bagus untuk tactile sensationnya
o contra lateral posterior column for the side contralateral to the lesions
o Contra lateral anterior spinothalamic tract for the side ipsilateral to it
- Selain long tract nya damage -> anterior horn cells juga bisa kena to variable extent at the level of lesions ->
flaccid paresis
- Irritation of posterior roots -> bisa bikin paresthesiae or radicular pain in the corresponding dermatomes at
upper borer o the sensory disturbance

CERVICAL ROOT LESIONS OF DEGENERATIVE ORIGIN

- Cervical radicular syndromes = sering banget gara2
foraminal stenosis of this type -> caused by
osteochondrosis
- End plate dari cervical vertebrae itu bagian pinggirnya itu
lebih elevated -> bikin proccesus ucinate -> jadi saddle like
structure -> kalo intervertebral disk degenerates ->
verbteral body atasnya bakal sinks like wedge into the
saddle like depression of the one below -> increases
pressure on the uncinate processes. -> bone remodeling ->
which uncinate processes gradually displaced laterally and
dorsally -> intervertebral foramina gradually become
narrower.
 - Cervical osteochondrosis sering di C5-C6, C6-C7, C3-4, C7-T1.
- Most common symptom:
o Segmental pain and paresthesiae, atrributable to nerve root irritation

INDIVIDUAL CERVICAL RADICULAR SYNDROME

- C3, C4 = pain in the neck and shoulder -> rarely partial diaphragmatic palsy
- C5 = pain with or without hypalgesia in the C5 dermatome, deltoid and biceps weakness
- C6 = pain with or without hypalgesia in the C6 dermatome, biceps and brachioradialis weakness; diminished
biceps reflex
- C7 = pain with or without paresthesia or hypalgesia in the C7 dermatome: triceps and pronator teres
weaknesS: possible thenar atrophy, diminished triceps reflex
- C8 = pain with or without paresthesia or hypalegsia in C8 dermatome: weakness and possibly atrophy of the
hypothenar muscles: diminished triceps and Tromner Reflex

LUMBAR RADICULAR SYNDROME

- L3 = pain with or without paresthesia in L3 dermatome, quadriceps
weakness, turun or absent quadriceps reflex (patellar or knee jerk)
- L4 = pain with or without paresthesia or hypalgesia in L4 dermatome,
quadriceps weakness, diminished quadriceps reflex
- L5 = pain with or without paresthesia or hypalesia in L5 dermatome,
weakness of extensor hallucis longus & extensor digitorum brevis, loss
of tibialis posterior reflex
- S1 = pain with or without paresthesia or hypalgesia in S1 dematome,
weaekness of peronei, gastrocnemius, seleus muscle, loss of
gastrocnemius reflex (Achiless)

NONSTEROIDAL ANTI-INFLAMMATORY DRUGS (NSAIDS)

- All mechanism dari obat NSAID sama, yaitu buat inhibit COX 1 or/and COX 2
o Yang selective khusus COX 2 inhibitor  karna COX 1 bersifat house-keeping yaitu untuk protect
mukosa lambung, mempertahankan tekanan glomerulus
o Kalo non-selective berarti COX 1 kehambat juga  produksi mukosa lambung turun dan mudah
iritasi, kalo prostaglyndin prostacyclin vasodilatasi bikin efferent vasokonstriksi jadi tekanan di
glomerulus tinggi  damage. Efek samping utama ke lambung = peptic ulcer dan ginjal nephropathy
- Kalo NSAID terlalu selective berbahaya:
o COX 1 and COX 2 supposed to be balance
o Kalo terlalu kuat COX 2 inhibitor  COX 1 yang punya fungsi produksi thromboxane A2 (untuk
stimulate thrombocyte aggregation) akan meningkat  agregasi thrombocyte meningkat 
pembekuan  stroke
- Kalo NSAID yang block both COX: COX 1 kehambat gada yang agregasi thrombocyte + dikasih obat pengencer
darah = FATAL
- Step-ladder management of pain (WHO)
1. Mild pain: NSAID +/- adjuvant (bisa
paracetamol/acetaminophen  NSAID golongan
beda karna menghambat prostaglandin di pusat
nyeri)
 2. Moderate pain: weak narcotic + NSAID (berperan sebagai adjuvant) + adjuvant (antipsychotic atau bisa
dikasih muscle relaxant)
3. Severe pain: strong narcotic + NSAID + adjuvant
4. Regional anesthesia: paling kuat
- Selective COX-2 inhibitors:
o Celecoxib
o Meloxicam
- Nonselective COX inhibitors:
o Diclofenac
o Ibuprofen
o Flurbiprofen
o Indomethacin
o Ketoprofen
o Nabumetone
o Naproxen
o Piroxicam

ACUTE PAIN PHYSIOLOGY AND ANATOMY

PERIPHERAL MECHANISM
- Primary afferent nociceptor
o Terdiri dari axon dari 3 jenis neurons
 Primary sensory afferents
 Motor neurons
 Sympathetic postganglionic neurons
o Primary sensory afferent
 Cell bodiesnya berada di Dorsal Root Ganglion, dengan 2 cabang axon, satu ke spinal cord,
satu lagi ke tissue untuk innervate
 Ada 3 jenis
 A- Beta :
o Largest diameter, myelinated
o Respond maximally to light-touch or moving stimuli
o Present PRIMARILY in nerves that innervates the skin
o Pada keadaan normal  tidak menimbulkan pain
 A- Delta :
o Small diameter, myelinated (cepat)
o Present in nerves to the skin, and to deep somatic and visceral structure
o CORNEA  hanya diinervasi oleh A delta dan C fiber
o Mostly respond maximally ONLY to intense (painful) stimuli  produce
subjective experience of pain saat stimulated
o Merupakan PRIMARY AFFERENT NOCICEPTORS (pain receptors)
o Substance: glutamate
 C fiber :
o Unmyelinated (lambat)  efek lebih lama dan mulai lebih lama (contoh:
kebakar)
o Bersama dengan A-Delta 
primary afferent nociceptors
o Substance P
  Individual primary afferent nociceptors can respond to several different types of noxious
stimuli. For example, most nociceptors respond to heat; intense cold; intense mechanical
stimuli, such as a pinch; changes in pH, particularly an acidic environment; and application of
chemical irritants including adenosine triphosphate (ATP), serotonin, bradykinin, and
histamine.
o Sensitization
 Saat terjadi stimuli yang intense, prolonged, dan repeated  threshold untuk aktifasi
primary affereny nociceptor diturunkan & frequency of firing dinaikkan ( inflammatory
mediator bradykinin, nerve-growth factor, prostaglandin, leukotriene berperan)  disebut
SENSITIZATION
 Sensitization bisa terjadi di peripheral nerve terminal (peripheral sensitization) dan Dorsal
horn of spinal cord (Central sensitization)
 Peripheral sensitization
 Terjadi ketika ada inflamasi atau injury pada tissue
 Inflammatory mediators activate intracellular signal in nociceptor
 Increase in production, transport, membrane insertion of chemically gated and
voltage gated ion channels
 Perubahan2 ini menyebabkan penurunan threshold dan meningkatkan excitability
dari nociceptor terminal melalui akifasi mekanikal, thermal, ataupun chemical
 Central sensitization
 Terjadi ketika aktifitas inflamasi meningkatkan excitatory dari nerve cells di dorsal
horn of spinal cord  producing pain
 Sensitization berperan dalam menciptakan : Soreness, tenderness, hyperalgesia (seakan2
pain stimulus lebih tinggi dari seharusnya) contoh : pada sunburnt skin akan terasa nyeri
ketika terkena gentle slap or warm shower
 Most A- Delta dan C fiber tidak akan aktif ketika tissue tidak injured atau inflamasi, tetapi
ketika terpapar oleh inflammatory mediator, Nerve2 tersebut aktif dan memberi rasa nyeri,
hal ini disebut “silent nociceptor”  ini yang menjelaskan kenapa deep structure yg
insensitive bisa terasa sakit ketika terjadi injury
o Nociceptor Induced Inflammation
 Primary afferent nociceptors juga punya efek neuroeffector, tidak hanya sensory saja
 Most nociceptors contain polypeptide mediators yang
akan dilepaskan dari peripheral terminal pada saat ter-
aktifasi (contohnya Substance P / SP)
 Substance P punya banyak guna seperti :
 Potent vasodilator
 Degranulate mast cells
 Chemoattractant for leukocytes
 Increase production and release of
inflammatory mediator
- 4 tahap:
1. Transduction
o Transduction begins when the free nerve endings (nociceptors) of C fibres and A-delta fibres of
primary afferent neurones respond to noxious stimuli.
o Three categories of noxious stimuli:
 mechanical (pressure, swelling, abscess, incision, tumour growth);
 thermal (burn, scald);
 chemical (excitatory neurotransmitter, toxic substance, ischaemia, infection).
o This noxious stimulation causes a release of chemical mediators from the damaged cells including:
 prostaglandin;
 bradykinin;
 serotonin;
 substance P;
 potassium;
 histamine.
o These chemical mediators activate and/or sensitise the nociceptors to the noxious stimuli. In order
for a pain impulse to be generated, an exchange of sodium and potassium ions (de-polarisation and
re-polarisation) occurs at the cell membranes. This results in an action potential and generation of a
pain impulse.

2. Transmission
o The transmission process occurs in three stages of transmission:
 from the site of transduction along the nociceptor fibres to the dorsal horn in the spinal
cord;
 from the spinal cord to the brain stem;
 through connections between the thalamus, cortex and higher levels of the brain.
o Impulse sakitnya lalu diteruskan ke thalamus dan brainstem via 2 jalur :
 spinothalamic pathway  utama di lateral
 spinoparabrachial pathway.
o The brain does not have a discrete pain centre, so when impulses arrive in the thalamus they are
directed to multiple areas in the brain where they are processed.
3. Perception
o The multidimensional experience of pain has affective-motivational, sensory-discriminative,
emotional and behavioural components.
o Saat impulse nyeri sampe thalamus dan otak, beberapa bagian otak akan berperan :
 The reticular system:
  Berperan dalam autonomic dan responds to pain (contoh tangan akan menjauh
ketika nyentuh panci panas)
 Berperan juga dalam affective-motivational response to pain (contoh melihat luka
yang terbentuk dan menilai lukanya)
 Somatosensory cortex:
 Berperan dalam perception and interpretation of sensations.
 Menilai intensity sakit, tipe sakit, atau lokasi dari sakitnya  dihubungkan dengan
past experiences, memory, dan cognitive activities.
 Menilai sakitnya dimana, sekuat apa sebelum menimbulkan response
 Limbic system:
 Berperan dalam emotional and behavioural responses to pain (contoh, attention,
mood, motivation, processing pain, dan mengingat past experiences dari rasa sakit
tersebut)
4. Modulating
o Modulation berperan dalam inhibisi atau mengubah pain stimulus di dalam spinal cord agar tidak
berlanjut
o Pathway yang berperan dalam modulating adalah : descending modulatory pain pathways (DMPP)
and these can lead to either an increase in the transmission of pain impulses (excitatory) or a
decrease in transmission (inhibition).
o Descending inhibition involves the release of inhibitory neurotransmitters that block or partially
block the transmission of pain impulses, and therefore produce analgesia

BUILT IN ANALGESIC SYSTEM

 Berperan dalam supress transmission of pain pathway di spinal cord
 Disebut juga Descending Analgesic Pathway, terdiri dari 3 brain stem region :
o Periaqueductal gray matter (gray matter disekeliling cerebral aqueductus of sylvii)
o Specific nuclei di medulla
o Specific nuclei di reticular formation
 Ketika bangunan2 diatas mendapat stimulasi  efeknya analgesic
 Periaqueductal gray matter stimulasi sel2 neuron di medulla dan reticular formation  stimulasi inhibitory
interneuron yang berada di dorsal horn spinal cord  inhibitory interneuron release endogenous opioids
(endorphins, enkephalins, dynorphin)  endogenous opioids nempel di mu opiate receptors di afferent
pain fiber terminal (ujung dari afferent pain fiber)  suppressed release of substance P via presynaptic
inhibition
 Morphine juga menempel pada opiate receptor di afferent pain fiber terminal  maka endogeneous opioid
berefek hampir sama dengan morphine

SPONDILYTIS TUBERCULOSIS (POTT’S DZ)

Peradangan granulomatous yg bersifat destruktif kronik pada vertebra oleh Mycobacterium Tuberculosis, Syphilis,
Actinomyces
Vertebrae yang paling sering kena:
- Thoracal: biasanya dari TB paru milier menyebar melalui para aorta flexus  biasa di anak
- Lumbal: dari GI tract / urinary tract TB  lewatin Batson’s plexus  biasa di adults
Spondylitis dibagi menjadi 3 bentuk berdasarkan lokasi :
- Central : Di tengah2 dari corpus vertebralis
- Paradiskus : Di corpus vertebra yang bertempelan dengan diskus intervertebralis
- Anterior : Kena bagian ant. Dari corpus vertebralis

Stadium:
1. Implantasi
a. Duplikasi bakteri 6 – 8 minggu
 b. Biasa terjadi pada paradiskus (dewasa) atau sentral (anak)
2. Destruksi awal
a. 3 – 6 minggu
b. Destruksi corpus vertebra dan penyempitan diskus
3. Destruksi lanjut (terbentuk gibbus)
a. Massive destruction  vertebral collapse
b. Casseous Mass and Cold abscess formation
c. Sequestrum + Destruction of vertebral body
d. Wedging anterior (kompresi bagian anterior)  kifosis / gibbus
4. Gangguan neurologis
a. Abscess tertekan menuju canalis spinalis (khususnya thoracalis karena memiliki canal yg sempit)
b. Derajat :
i. I : Kelemahan ekstremitas bawah terjadi setelah aktifitas berat, belum ada gangguang
sensory
ii. II : Kelemahan ekstremitas bawah, masih dapat bekerja
iii. III : kelemahan ektremitas bawah sampai membatasi gerakan, bisa hipestesi atau anestesi
(mati rasa atau sakit berlebih)
iv. IV : gangguan sensoris + motoris dengan gangguan urination and defecation
5. Deformity
a. Gibbus permanen (kerusakan permanen di corpus vertebralis)

M. Tuberculosis bisa masuk ke Corpus vertebralis melalui hematogenous spread ATAU Venous Plexus of Batson 
menyerang pada bagian anterior Corpus vertebralis (anak2 biasa kena disc karena banyak pembuluhnya) 
proliferasi bakteri di vertebrae  infection and destruction of corpus vertebralis  anteriorly compressed  Gibbus
 spinal canal compression  neurological effect and Lower motor deficit  Numbness and weakness of both
lower extremities  POTTS PARAPLEGIA
Gejala klinis:
- Vertebrae pain
- Paravertebral muscle spasm
- Nyeri ketika movement
- Paralysis
Pemeriksaan:
- X-ray: TB paru -> infiltrat pada apex / ujung atas
- Vertebrae -> lihat sequestrum
- Mantouk Test -> nyuntikkin tuberculosis yang sudah di lemahkan -> diliat setelah 48 jam diliat ada benjolan
ga  dewasa positive yg awalnya kecil berubah 15 mm . Positive di anak-anak jadi 10 mm.
- Basil Tahan Asam
Treatment:
- OAT (obat anti tuberculosis)
o R: Rifampicin (5 mg/kg BB/24 jam)  bikin pipis merah kaya darah
 o H: Isoniazid (10 mg)  bikin kekurangan vit B6, saraf di ujung2 neuritis
o Z: Pirazinamid (25)  hepatotoxic
o E: Etam Butol (15)  komplikasi bikin buta warna
o S: Streptomycin (15)  bikin budeg
- Kategori 1 -> untuk semua kasus baru yg tidak ada riwayat sebelumnya
o minimal 6-8 bulan
o 2 RHZE (2 bulan pertama minum 4 obat)/ 4 RH (bulan ke 4 seterusnya minum 2 obat)  PDPI: 2RHZE
/ 10RH
o 2bulan pertama RHZE / 4bulan kemudian R3H3 (cuma 3x seminggu)
o 2RHZE / 6 RE
- Kategori 2 ( 8 bulan ) -> untuk pasien yang kategori 1 gak mempan atau untuk pasien yang putus pengobatan
o 2 RHZE / 1 RHZE / 5 RHE
 - GABA: inibit depol dengan masukin Cl
- Glutamate: induce depol dengan masukin Na, Ca
AUTONOMIC NERVOUS SYSTEM
Definition: nervous system that controls most visceral functions of
the body.  helps to control arterial pressure, gastrointestinal
motility, gastrointestinal secretion, urinary bladder emptying,
sweating, body temperature (bisa controlled entirely or partially)
- Karakteristik: rapidity and intensity dimana bisa ubah visceral
functions (cth. Within 3-5 s bisa increase heart rate to 2x
normal)
General organization:
- Activated by centers located in spinal cord, brain stem, and
hypothalamus
o Limbic cortex bisa transmit signals ke lower centers
- Efferent autonomic signals transmitted ke organ via =
sympathetic nervous system and parasympathetic nervous
system
Sympathetic nervous system
- Sympathetic nerve fibers originate in spinal cord between
segments T1-L2 and pass into sympathetic chain  tissue
and organ
- Each sympathetic pathway from cord to tissue is composed
of 2 neurons = preganglionic neuron and postganglionic
neuron
o cell body of each preganglionic neuron ada di
intermediolateral horn of spinal cord  fibernya
pass thru ventral root into corresponding spinal
nerve
o abis spinal nerve leaves spinal canal  preganglionic
fibers leave spinal nerve terus pass thru white ramus
into one of the ganglia di sympathetic chain.
 Synapse with postganglionic sympathetic
neurons di ganglion yang dimasukin
 Pass upward or downward in chain terus
synapse in one of other ganglia
 Pass distance thru the chain terus thru one of
sympathetic nerves radiating outside the chain
 synapse di peripheral sympathetic ganglion
o Postganglionic sympathetic neuron originates either di
one of sympathetic chain ganglia or peripheral
sympathetic ganglia.  baru ke organ

Parasympathetic nervous system

- Parasympathetic fibers leave CNS thru CN III, VII, IX, X (75%) or
thru 2nd and 3rd and occasionally 1st and 4th sacral nerves.
o 75% CN X  pass to entire thoracic and abdominal
regions: heart, lungs, esophagus, stomach, entire small
intestine, proximal half of colon, liver, gallbladder,
pancreas, kidneys, upper portion of ureters.
o CN III  pupillary sphincter and ciliary muscle of the
eye
o CN VII  lacrimal, nasal, submandibular glands
o CN IX  parotid gland
 o Bagian sacral (pelvic nerves) di S2 and S3  descending colon, rectum, urinary bladder, lower
portions of ureters, external genitalia (erection)
- Ada both preganglionic and postganglionic neurons
o Preganglionic fibers bisa langsung ke organ
o Postganglionic neurons ada di wall of organ
Functions
- 2 synaptic transmitter
o acetylcholine = cholinergic
o norepinephrine = adrenergic
- preganglionic neurons  cholinergic di both systems. Acetylcholine kalo di apply ke ganglia bakal excite both
sympathetic and parasympathetic postganglionic neurons
o either all or almost all of postganglionic neurons of parasympathetic system = cholinergic 
parasympathetic transmitter
o most of postganglionic sympathetic neurons =
adrenergic  sympathetic transmitter
 fibers yang ke sweat glands dan sedikit
vessel = cholinergic
- sympathetic nervous system:
o promotes fight-or-flight response  arousal and
energy generation, and inhibits digestion
o vasoconstriction
o dilates bronchioles of lung thru circulating
epinephrine  greater alveolar oxygen exchange
o increase heart rate and contractility of cardiac
cells (myocytes)  enhanced blood flow to
skeletal muscle
o dilates pupils and relaxes the ciliary muscle to
lens  more light to enter the eye and far vision
o vasodilation for coronary vessels of the heart
o constricts all intestinal sphincters and urinary
sphincter
o inhibits peristalsis
o stimulates orgasm
- parasympathetic nervous system:
o promotes rest and digest response  enhance
digestion, calming the nerves
o dilate blood vessels to GIT, increase blood flow
setelah makan  metabolic demands
o constrict the bronchiolar diameter when need for oxygen udah berkurang
o constrict of pupil and ciliary muscle  closer vision
o stimulates salivary gland secretion and accelerates peristalsis
o sexual  stimulates sexual arousal
MRI FOR POTT’S DISEASE
MRI is done by taking noncontrast T1-weighted (T1W), T2-weighted (T2W), and short tau inversion recovery (STIR)
sequences in axial, sagittal, and coronal planes followed by contrast-enhanced T1W sequences after intravenous
administration of gadolinium contrast agent. MRI features of Pott's spine are abnormal signal intensities appearing
hypointense on T1W and hyperintense on T2W sequences with heterogeneous enhancement of the vertebral body.
STIR sequences are helpful in differentiating fluid from fatty component in non-contrast sequences. Characteristic
findings included destruction of two adjacent vertebral bodies and opposing end plates; destruction of intervening
disc; vertebral body edema; and occurrence of prevertebral, paravertebral, and epidural abscesses. MRI plays an
important role in the diagnosis of spinal TB with a high specificity and sensitivity