DALAM APLIKASI KLINIS NEUROLOGIS

Prof BOB SANTOSO WIBOWO SpS(K)

Subdiv. EMG & EVOKED POTENTIALS Dept. of NEUROLOGY FKUI / RSUPN CM

NEUROSAINS

is a field that is devoted to the scientific study of the nervous system. Such studies span the structure, function, evolutionary history, development, genetics, biochemistry, physiology, pharmacology, informatics, computational neuroscience and pathology of the nervous system. Traditionally it is seen as a branch of biological sciences. However, recently there has been a surge in the convergence of interest from many allied disciplines, including cognitive and neuro-psychology, computer science, statistics, physics, and medicine.
http://en.wikipedia.org/wiki/Neuroscience

Neuroscience

The scope of neuroscience has now broadened to include any systematic scientific experimental and theoretical investigation of the central and peripheral nervous system of biological organisms.
The methodologies employed by neuroscientists have been enormously expanded, from genetic, biochemical and analysis of dynamics of individual nerve cells and their molecular constituents to imaging representations of perceptual and motor tasks in the brain.
http://en.wikipedia.org/wiki/Neuroscience

Neuroscience

is at the frontier of investigation of the brain and mind.

The study of the brain is becoming the cornerstone in understanding how we perceive and interact with the external world and, in particular, how human experience and human biology influence each other.
The Neuroscience Program. Amherst College. Retrieved on 2008-04-15. http://en.wikipedia.org/wiki/Neuroscience

Every school has its own way of teaching neuroscience

Consequently, the order in which information is presented , varies inormously Although taught in logical sequence, the student can enter at any point as a starting point of any given subject

This is just a brief account of the organization and functions of nervous tissue, with pariticular emphasis on the normal human nervous system

Many abnormalities are also discribed A they provide the only clues indicating the normal functions of some parts of the human brain B the correlation between the functional deficits and the pathological anatomy in some diseases , to illustrate important facts of neuroanatomy C several neurological diseases, are common enough to justify inclusion in any general text of neuroscience D the intelligent diagnosis and clinical management of these conditions demand a working knowledge of the relevant anatomy and physiology

Neurologi klinik
Penerapan ilmu-ilmu neurologi utk mempelajari fenomena-fenomena perubahan berbagai aspek susunan saraf dalam kaitannya dng berbagai gangguan terhadap susunan saraf pusat dan perifer baik secara primer maupun sekunder.

Overview Sistim Saraf Pusat dan Perifer

Organisasi Sistem Persarafan

Sistem saraf pusat otak dan medulla spinalis Sistem saraf perifer - Serabut saraf (dan ganglia) membawa informasi dari kulit dan tingkai (afferen) - Serabut saraf membawa informasi ke otot-otot untuk mengontrol gerakan (efferen) - Serabut saraf dan ganglia sistem saraf otonom - Serabut saraf dan ganglia dari sistem persarafan enteric untuk mengontrol fungsi usus

Susunan Saraf Pusat

Otak Medula Spinalis

Overview

Serebrum
Serebellum Batang otak

- Bagian dari SSP yang mengatur dan mengisi kesadaran

Diencephalon - Pintu gerbang informasi sensorik menuju serebrum. - berfungsi mengontrol fungsi motorik. membawa informasi ke dan dari medula spinalis serta

berfungsi sebagai kontrol motorik kepala dan leher.

Spinal Cord Organization

Gray matter: mostly cell bodies

Dendrites & terminals Spinal reflex integrating center

White matter

Bundles of myelinated axons

Ascending tracts sensory Descending tracts motor

Dorsal roots Ventral roots

Neuron Numbers and Types

The Brain has enormous numbers of computing elements (neurons) that accomplish sophisticated computation because of their large numbers, extensive inter-connections, and their high degree of specialization into different types of neurons
(Jan S. Purba MD, PhD)

The Basic Action of the Neuron

Neurons have direct actions and indirect actions Direct actions take only one of two forms: to excite or to inhibit Indirect actions can occur in several ways, but the important consequence is that they modulate excitatory or inhibitory activity
(Jan S. Purba MD, PhD)

(Jan S. Purba MD, PhD)

(Jan S. Purba MD, PhD)

Action potentials

A resting neuron maintains a resting electrical charge, relative to the outside fluids When a neuronal membrane is destabilized, either by an appropriate electrical field or reaction with neurotransmitter chemical, the resting membrane potential reverses polarity This polarity reversal propagates from point along the membrane surface
(Jan S. Purba MD, PhD)

Calcium and Transmitter Release

Calcium entry couples action potentials to neurotransmitter release In many synapses, depolarization of presynaptic terminals opens the membrane gate for calcium channels influx, which in turn triggers the release of certain transmitters These channels are voltage sensitive, unlike the classes of membrane channels that are ligand sensitive

(Jan S. Purba MD, PhD)

Neurochemical Transmission

Neurons release transmitter chemical secretions from their terminals into synapses, which serve to excite or to inhibit postsynaptic cells Synaptic transmission is ultimately associated with altered conductance across the membrane of specific ions
(Jan S. Purba MD, PhD)

lanjutan

Neurochemical Transmission

The conformational changes and channels opening are regulated by membrane potential changes in some ion channel systems and by specific neurotransmitterreceptor interactions in other systems (ACh and GABA, for example) Neurotransmitters affect virtually all physiological processes in the brain and all behaviors, and any given process or behavior is generally influenced by more than one neurotransmitter or neuromodulator
(Jan S. Purba MD, PhD)

Neuronal Transport
Neurons transport metabolic products, sometimes over relatively great distances, through small cytoplasmic extensions of the cell body
(Jan S. Purba MD, PhD)

Neuronal Targets

The growing processes of neurons are guided to their targets by physical forces in their environment and chemical signals emitted by the targets
Depriving a neuron of contact with its normal contact may cause the neuron to degenerate or die and its targets to become supersensitive to the chemical secretions of the missing neuron
(Jan S. Purba MD, PhD)

Ending Neurotransmission
The action of released transmitter is terminated by several mechanisms: enzymatic destruction diffusion away from receptors and active transport processes that take the transmitter or its precursors back into nerve terminals or into adjacent glia cells
(Jan S. Purba MD, PhD)

Presynaptic Neuron
Synaptic Vesicles
DA DA DA

Postsynaptic Neuron
Receptors

DA

MAO

NE NE NE

NE

MAO

5-HT 5-HT 5-HT

5-HT

NE = norepinehrine 5-HT = 5 hydroxytryptamine (serotonin) DA = dopamine MAO = monoamine oxidase Adapted from Richelson E. Mayo Clinic Proceedings 1994

(Jan S. Purba MD, PhD)

Membrane Receptors

Neural membranes, both presynaptic and postsynaptic, contain embedded proteins that act as receptors for specific ligands

These ligands are normally neurotransmitters and hormones, but they can also be drugs The ligands must fit the conformation and electric charge properties of their receptors
(Jan S. Purba MD, PhD)

lanjutan

Membrane Receptors

This means that the ordering of amino acids in the receptor protein is very important, along with the ordering of constituent atoms in the transmitter and the arrangement of atoms in space (i.e., the handedness of certain key atoms) When a ligand binds a receptor, the receptor molecule changes conformation, which may in turn changes the channels in receptor protein that allow ions to flow across the cell membrane
(Jan S. Purba MD, PhD)

Receptor Binding

Neurotransmitters bind receptors temporarily, because the interactions do not lead

to covalent bonds but rather are a combination of weaker forces involving hydrogen bonding, electrostatic attraction and Van der Waals forces

Such binding is stereo specific and confers a particular conformation on the membrane receptor This receptor conformation determines whether the aqueous channels within the protein are open or closed to ionic flux
(Jan S. Purba MD, PhD)

Ion Channels

Neuronal membranes have coiled proteins that are embedded in the hydrophobic lipid bilayer

Some of the amino acids

surround a variable-size pore, which constitutes a channel through which ions can flow according to the electrostatic and concentration gradients
(Jan S. Purba MD, PhD)

lanjutan

Ion Channels

The degree to which these ion channels are open can be regulated by voltage fields (voltage-gated channels) Voltage-gated channels, at least those for sodium in mammalian brain, are also regulated by phosphorylation of protein kinase C and cAMP-dependent protein kinase
(Jan S. Purba MD, PhD)

Schematic illustration of the signaling pathways

Discovered or characterized in the neurodegenerative disease program that can be targeted to prevent neuronal apoptosis and thus treat various neurological disease. Drug or molecular therapies are being developed to : (1) antagonize NMDA receptors (NMDA-Rc), (2) modulate activation of the p38 mitogen activated kinase (MAPK)-MEF2C (transcription factor) pathway, (3) prevent toxic reactions of free radicals such as nitric oxide (NO) and reactive oxygen species (ROS), and (4) inhibit apoptosis-inducing enzymes including caspases

(Jan S. Purba MD, PhD)

(Jan S. Purba MD, PhD)

(Jan S. Purba MD, PhD)

apoptosis

(Jan S. Purba MD, PhD)

Second Messengers

Activation (opening) of an ion channel creates a cascade of intracellular biochemical reaction that leads ultimately to phosphorylation of intracellular proteins
This cascade of reactions constitutes a biochemical signal transduction mechanism that converts biochemical signals at membrane surface to biochemical signal inside the cell
(Jan S. Purba MD, PhD)

The roles of calcium and cytochrome C as interorganellar messenger in

apoptosis

Cytochrome c released from mitochondria functions in a positive feedback loop by binding to InsP3 receptors on the endoplasmic reticulum, triggering calcium release (Jan S. Purba MD, PhD) and thus amplifying calcium-dependent apoptosis

Plasticity

The nervous system can exhibit considerable plasticity Neurons can grow new axonal and dendritic processes, and new synapses can be formed Moreover, neural circuits can be recruited into existence and exiting circuits can be re-organized Even certain topographical maps can be sculpted by the nature of their input
(Jan S. Purba MD, PhD)

Neurologi Klinik

Metodologi dalam

Mengaplikasikan neuroanatomi, neurofisiologi, neuropatologi, neurokimia, neuroimaging dan fungsi susunan saraf pusat dan perifer baik dalam keadaan sehat maupun sakit untuk menegakkan diagnosis dan mengaplikasikan penemuan neurofarmakologi, neurobehaviour, neurorehabilitasi dalam rangka pengobatan/penyembuhan penderita.

Metode
1.

Anamnesis Menggunakan metode wawancara baik dengan penderita (auto) maupun dengan orang-orang yang dekat dengan penderita (allo) Wawancara ini sangat penting dan utama kelihaian seorang dokter terlihat dari penguasaan komunikasi dan ketajaman naluri dalam mencari penyakit penderita Anamnesis yang akurat gambaran diagnosis atau diagnosis banding dapat ditemukan

2.

Pemeriksaan/status neurologi klinik

A.

Pemeriksaan umum, meliputi pemeriksaan fungsi vital dan gambaran umum dari kepala, dada dan perut serta ekstremitas

A.Pemeriksaan Neurologi
Meliputi: Pemeriksaan Kesadaran I. Kuantitas; dapat digunakan Skala Koma Glasgow dengan menilai respon mata, motorik, verbal. II. Kualitas - Meningkatnya tingkat kesadaran/eksitasi serebral: tremor, euforia, mania - Menurunnya tingkat kesadaran: delirium, somnolen, sopor, soporokoma, koma

GLASGOW COMA SCALE

Verbal Motor Eyes

Verbal

Orientasi baik (5) Bingung (confused) (4) Bicara tidak sesuai (inappropriate) (3) Suara tidak dimengerti (2) Tidak ada suara (1) (T=intubasi)

Motor

Bergerak sesuai perintah (6) Melokalisai nyeri (5) Fleksi terhadap nyeri (withdrawal) (4) Fleksi abnormal (3) Respons ekstensi (2) Tidak ada respon (1)

Eyes

Buka mata spontan (4) Buka mata dengan perintah (3) Buka mata dengan rangsangan nyeri (2) Tidak ada respon (1)

 Pemeriksaan

Rangsang Meningeal

- Kaku - Tanda - Tanda - Tanda - Tanda

Kuduk Lasegue Kernig Brudzinski I Brudzinski II

Saraf Kranialis

 Pemeriksaan fungsi saraf kranialis

Pemeriksaan fungsi saraf kranialis

Pemeriksaan Motorik
Homunculus Motorik

Traktus Kortikospinal

Voluntary Movement: Conscious

Pemeriksaan Sistem Motorik

Meliputi
-

Kekuatan motorik Tonus (hiper, normo dan hipo) Trofik (hiper, normo dan hipo) Gerakan-gerakan involunter

Kekuatan motorik

Pemeriksaan Sistem Sensorik

Meliputi: - Pemeriksaan sensorik - Eksteroseptif (nyeri, raba/tekan, suhu) - Proprioseptif - Enteroseptif

General Properties of Sensory Systems

Homunculus Sensorik

Jaras sensorik

Refleks-Refleks :
-

Refleks Fisiologis (Biseps, Triseps, KPR, APR) Refleks Patologis (Babinsky, Chaddock, dll)

Pemeriksaan fungsi vestibuler dan serebelum Pemeriksaan fungsi kortikal luhur jika diindikasikan seperti: - TOAG (Test Orientation and Attention of Galvaston) - MMSE (Mini Mental Status Examination), penilaian awal fungsi kognitif

Diagnosis dan Diagnosis Banding

Kesimpulan dari semua pemeriksaan adalah diagnosa atau diagnosa banding (jika belum jelas kesimpulan pemeriksaan tsb). Dan berdasar diagnosis tersebut disusun rancangan pemeriksaan tambahan/penunjang untuk lebih memastikan diagnosis sekaligus menyingkirkan diagnosis banding.

Pemeriksaan Tambahan/Penunjang
Meliputi :

Pemeriksaan laboratorium umum/khusus/LP Pemeriksaan neuroimaging konvensional CT scan, MRI, MRS, PET, SPECT Pemeriksaan khusus atas indikasi EEG-Brain Mapping, EMG, Evoked potential, Doppler, Neurooftalmologi, Neurootologi

Tromner reflex hammer

BABINSKI TELESCOPING REFLEX HAMMER

This is not a reflex hammer

EEG

http://www.polysomnograph.com/images/mapping.png

TOP VIEW

Human Brain Mapping and Neuroimaging Research

are new multidisciplinary fields that demand * novel statistical models and * analytic tools for quantifying disease, * temporal, age, genotypic and neurophysiological variation in the brain anatomy and function. www.stat.ucla.edu

The future of quantitative EEG for clinical applications lies,

undoubtedly, in the coupling of digital methods of signal analysis and of image processing. In this picture, what you see is the combination of two remarkable devices: the magnetic resonance scanner (MRI), which produces anatomical or functional images of the brain with great detail and

clarity, and the magnetoencephalograph (MEG). The MEG is capable of recording minute alterations in the electromagn generated by the electrical activity of neurons deep within the brain. In order to do this, it uses a magnetic pick-up coil immersed into liquid named SQUID, thus achieving the phenomenon of electrical supercondu The resulting record is superimposed upon the anatomical image generated by the MRI scanner. In this figure, points of altered electrical activity (epileptic areas) are shown as colored circles, placed over the areas where the MEG apparatus was able to determine its location. The increased sophistication and number of resources available on computerized EEG systems and of medical imaging processing will continue to evolve. Quantitative, high resolution EEG has a bright future as a tool in the medical diagnostic work-up.

http://www.tc.umn.edu/~binhe/cit.htm

http://splweb.bwh.harvard.edu:8000/~hjpark/Snapshots/PET_MRI_EEG.jpg

EMG

Terapi / Pengobatan
Meliputi Pengobatan kausal Pengobatan simptomatik Pengobatan kognitif dan neurorehabilitasi

Ilustrasi kasus aplikasi neurologi klinis

Seorang laki-laki berusia 60 tahun datang ke dokter dg keluhan utama nyeri kepala dan sempoyongan yang muncul tiba-tiba. Sebelumnya ia merasakan kelopak mata kanannya jatuh dan sukar menelan makanan. Selain itu suaranya juga menjadi serak. Pasien memiliki kebiasaan merokok sejak lama dan konsumsi alkohol > 3 botol setiap hari RPD: Hipertensi. Minum obat tidak teratur

PF: Tekanan darah meningkat, RR & HR dbn. Ptosis mata kanan, pupil anisokor kiri<kanan, refleks cornea (-) mata kanan, sensasi nyeri pada sisi kanan wajah, anhidrosis sisi wajah kanan, uvula deviasi ke kiri, palatum kanan jatuh, motorik kekuatan normal, sensasi tajam pada sisi tubuh kiri

KEGAGALAN ELEKTRIK KEGAGALAN ENERGI JARINGAN KEGAGALAN HOMEOSTASIS KATION SHIFT NEUROTRANSMITTER & KALSIUM

KEGAGALAN METABOLIK INTRASEL TOKSISITAS Ca

INFARK & NEKROSIS

KEGAGALAN ELEKTRIK
KEGAGALAN ENERGI JARINGAN OKSIGEN & GLUKOSA JAR. ATP & PCr ASIDOSIS LAKTAT JAR. KALIUM SELULAR Na,Ca2+, Cr, H2O SELULAR
TERJADI EDEMA SITOTOKSIK

MENURUNNYA HOMEOSTASIS KATION

PERGESERAN NEUROTRANSMITTER & Ca2+

PELEPASAN GLUTAMAT & NEUROTRANSMITTER LAIN INFLUX KALSIUM

KEGAGALAN METABOLIK

TOKSISITAS CALSIUM EKSTRASELULAR

INFARK DAN NEKROSIS

FOSFOLIPASE AS. ARAKHIDONAT LEUKOTRIN & PG RADIKAL OKSIGEN MERUSAK MEMBRAN PROTEIN & DNA PROTEASE MEMECAH PROTEIN ARGININ CITRULIN & NO

KERUSAKAN BBB EDEMA VASOGENIK (INTRASEL EDEMA) AKTIVITAS & RECRUITMENT LEKOSIT

The Molecular Events Initiated in Brain Tissue by Acute Cerebral Ischemia

Anaerobic Glycolysis

Anoxic Energy Protein Metabolism Depolarization sintesisi is damaged of membrane cell

CMRG=Cerebral Metabolic rate of Glucose

Kelainan Medulla Spinalis

Gejala & Tanda Klinis Lesi Medulla Spinalis:

1.

Tanda motorik
A.

B.

Tanda LMN : atrofi, hipotoni, hiporefleks, refleks patologik (-), klonus (-). Tanda UMN : hipertoni, hiperefleks, klonus (+), refleks patologik (+).

2.

Gejala nyeri
A.

B.

Nyeri Radikular: nyeri seperti ditusuk, pada distribusi dermatom saraf bagian dorsal inflamasi atau kompresi saraf dorsal yang disebabkan lesi ekstramedular medula spinalis. Menyebar, nyeri menetap lesi intramedular.

3.

Gejala sensorik
A.

B.

Nyeri & suhu: lesi pada traktus spinothalamikus defisit pada tubuh kontralateral dibawah lesi. Posisi & rasa getar defisit ipsilateral dan dibawah level lesi.

Sindroma klinis medula spinalis

1. 2.

3. 4.

Mielopati transversa : tanda LMN & UMN trauma, mielitis viral, MS. Hemiseksi medula spinalis sindroma Brown-Sequard gangguan nyeri & suhu kontralateral, kelemahan ipsilateral serta gangguan getar dan posisi trauma, tumor. Siringomielia gejala LMN setinggi lesi , paraparesis kongenital. Oklusi arteri spinalis anterior hiperefleks, paraparesis spastis, hilangnya rasa nyeri & suhu dibawah lesi aterosklerotik aorta.

5.

Subacute combined degeneration (sklerosis

6.

7.

posterolateral) hilangnya rasa getar & posisi pada tungkai bilateral berhubungan dengan tanda UMN defisiensi vit B 12. Amyotrophic Lateral Sclerosis (ALS): LMN & UMN etiologi belum diketahui. Tabes Dorsalis: nyeri, parestesia, hilangnya rasa getar & posisi Neurosifilis.

Lesi Saraf Perifer

Gejala sensorik lesi saraf perifer. Gangguan: - distal dng pola glove - stocking polineuropati. Klasifikasi:
A. B. C.

Mononeuropathy simplex Mononeuropathy multiplex Polyneuropathy GBS, CIDP,

metabolik (DM).

Lesi pada root & plexus:

A.

B.
C.

Lesi trauma & kompresi Tabes dorsalis Penyakit Lyme Siringomielia

Mielopati:
A.

B.

Subacute combined degeneration (defisiensi Vit B12)

Neuroscience

is at the frontier of investigation of the brain and mind.

The study of the brain is becoming the cornerstone in understanding how we perceive and interact with the external world and, in particular, how human experience and human biology influence each other.
The Neuroscience Program. Amherst College. Retrieved on 2008-04-15. http://en.wikipedia.org/wiki/Neuroscience