Transcript Neuromuscular Localization

Sistem Neuromuskular
Sistem Neuromuskular
Tiga komponen utama Neuromuskular
 Nerve
 Neuromuscular junction
 Muscle
Upper Motor Neuron
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Semua neuron yang menyalurkan impuls
motorik secara langsung ke LMN atau
melalui interneuronnya, tergolong dalam
kelompok UMN. Neuron-neuron tersebut
banyak terdapat di girus presentralis
dinamakan juga korteks motorik. Melalui
aksonnya neuron korteks motorik
menghubungi motoneuron di kornu
anterior medulla spinalis.
Area Motorik
Upper motorneuron
Lower motorneuron
Lower Motor Neuron
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Merupakan neuron-neuron yang
menyelurkan impuls motorik pada bagian
perjalanan terakhir (kornu anterior medula
spinalis) ke sel-sel otot skeletal.
Motor end Plate
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Pada ujungnya setiap akson akan
bercabang-cabang dan setiap cabang
menghubungi membrane serabut otot.
Serabut-serabut otot setiap unit motorik
berkisar antara 10-500 serabut otot. Tiap
serabut otot memilki satu “motor end
plate”.
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Ujung-ujung terminal dari akson
mengandung mitokondria dan ezim “cholin
acertyltransferase”, yang diperlukan untuk
sintesis “neurotransmitter” yang
dinamakan “acetylcholine”.
Pelepasan Acetilkolin
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Nerves releasing Achetylcholine at the
neuromuscular junction (=end plate) cause
the contraction of skeletal muscle. The
functional unit of a muscle organ is the
muscle fiber (=muscle cell).
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The muscle fiber contracts in an "all-ornone" fashion when stimulated by an
action potential. The action potential first
causes intracellular Ca++ release from the
sarcoplasmic reticulum and the Ca++
activates a cascade of events which
results in the movement of actin over
myosin (=sliding filament theory).
Tanda-tanda
kelumpuhan UMN :
• Hiperrefleksia
• Terdapat refleks
patologis
• Tonus otot meninggi
atau hipertonia
• Terdapat Klonus
• Tidak terdapat atrofi
otot yang lumpuh
• Refleks automatisme
spinal (-)
Tanda-tanda
kelumpuhan LMN :
• Arefleksia (hilangnya
refleks tendo)
• Tidak ada refleks
patologis
• Hilangnya tonus otot
(flacid)
• Tidak terdapat klonus
• Terdapat atrofi pada
otot yang lumpuh
Gangguan yang menyebabkan kelemahan
gerak (paralysis)
Kelainan pada otot
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Periodik Paralysis
Inflamatory miopathy
Miopati karena steroid
Rabdomyolisis
Neuromuscular junction
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Miastenia Gravis
Botulism
Tick paralysis
Lambert Eaton Myastenic Syndrome
Gangguan yang menyebabkan kelemahan
gerak (paralysis)
Neuropati akut
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Paraneoplastik
Vaskulitis (lupus, poliarteritis)
Neuropati motorik multifokal
Poliradikulopati akut
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Guillain-Barre syndrome
Lime Disease
Sindrome Cauda Equina
Penyakit Motor neuron
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Poliomyelitis
Amyotropic Lateral Sclerosis (ALS)
Gangguan yang menyebabkan kelemahan
gerak (paralysis)
Medula Spinalis
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Inflamasi (mielitis transversus)
Mielopati (spondilosis, hematom, infark)
Otak (Cerebrum, cerebellum)
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Lesi di Pons
Lesi fokal/multifokal (infark, hematom)
Jenis Gangguan Saraf
Polyneuropathy: motor, sensory,
sensorimotor
 Radiculopathy
 Polyradiculopathy
 Plexopathy
 Mononeuropathy: isolated
multiplex
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Klasifikasi kausa
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Toxic
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GBS, CIDP
Vasculitis
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Infective
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Drugs, alcohol,
organophosphates
Inflammatory/Immune
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Leprosy, Lyme, HIV,
Diphtheria
Traumatic
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Inherited
 HMSN and HLPP
 Amyloid
Metabolic
 Diabetes
 Vitamins: B12, B1, E
 Dialysis, Liver failure
Paraneoplastic
 sensory (anti-Hu)
Klasifikasi tipe kerusakan
Demyelinating
 Axonal
 Small fibre
 Large fibre
 Autonomic
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Physical findings
Nerve
NMJ
Muscle
Reflexes
Usually decr.
NL or decr.
NL or decr.
Atrophy
Can be severe
Minimal
Variable
Fascic.
Sometimes
None
None
Sensory loss Sometimes
None
None
The Motor Unit
Myopathies
Motor Neurone
Disorders
Peripheral Neuropathy
Myasthenia etc
Gangguan pada saraf:
Variasi:
 Cell body, axon & myelin
 Fiber size: large, small
 Motor, sensory, autonomic
 Distribution: focal, multifocal, generalized
 Course: acute, subacute, chronic, lifelong
 Etiology: genetic, toxic, metabolic,
autoimmune, traumatic, vascular, infectious
Gangguan pada Saraf:
berdasarkan Lokasi
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Radix
Plexus
Single nerve
Several nerves
radiculopathy
plexopathy
mononeuropathy
multiple mononeuropathy,
mononeuritis multiplex
polyneuropathy
All nerves,
length-dependent
All nerves,
polyradiculoneuropathy
not length-dependent
Radix
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Segmental loss of
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motor
 atrophy
 weakness
reflexes
 sensation
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Signs usually minimal; symptoms can
be severe (pain);
 Usually only one limb.
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Plexus
Pain
 Weakness, atrophy, variable, but
usually more severe than radiculopathy
 Usually restricted to one limb
 Etiology:
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Brachial: trauma, neoplasm, idiopathic
 Lumbosacral: diabetes, neoplasm
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Single nerve (mononeuropathy)
Restricted distribution
 Pain, numbness or tingling,
atrophy, weakness
 Etiology:
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entrapment
 trauma
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Carpal tunnel syndrome
N.Medianus
 Pain in hand,
forearm, arm
 Numbness in
median distribution
 Symptoms
aggravated by wrist
flexion
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Ulnar neuropathy
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Numbness
Atrophy of first dorsal
interosseous
Weakness
Compression at
elbow
Entrapment in cubital
tunnel
Distal injury
Radial nerve: Saturday night palsy
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Weakness of wrist &
finger extensors,
brachioradialis
Pressure palsy
Trauma (humerus
fracture)
Peroneal palsy
Crossing legs
 Weight loss
 Hospitalization
 Surgery
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Several nerves (mononeuritis multiplex)
Often painful at onset
 Often sudden
 Deficits in the distribution of several
peripheral nerves (one at a time)
 Etiology: vasculitis
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All nerves: Length-dependent
(polyneuropathy)
Lower before upper extremity
 Distal first (feet)
 Atrophy of intrinsic foot muscles
 Decreased ankle jerks
 Stocking, then glove sensory loss
 Distal motor and sensory findings
always much more severe than
proximal
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Polyneuropathy (cont’d)
Polyneuropathy (cont’d)
Most common kind of neuropathy
 Etiology
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metabolic (diabetes, renal failure)
 nutritional (thiamine, B12 deficiency)
 toxic (heavy metals, organic solvents,
some drugs)
 familial (Charcot-Marie-Tooth)
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All nerves, not length-dependent
(polyradiculoneuropathy)
Both proximal and distal weakness
 Variable sensory symptoms
 Autonomic symptoms (pulse, blood
pressure, urination...)
 Can affect respiration, swallowing
 Autoimmune
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Guillain-Barré Syndrome (GBS)
Merupakan penyakit Autoimmun
Definisi GBS :
 Penyakit demyelinasi akut, yang terutama
mengenai susunan saraf tepi. Penyakit
inflamasi pada sistim saraf tepi mempunyai
karakteristik adanya infiltrasi limfosit dan
makrofag dengan destruksi myelin
 Derajad dan lokasi kerusakan tergantung
saraf yang bermyelin: Motorik
Guillain-Barre syndrome
Progresses over days to <4 weeks
 Typically ascending weakness
 Reflexes lost early
 Motor symptoms predominate, but can
affect sensation and autonomic function
 Respiratory failure requires support
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Guillain-Barre syndrome (cont’d)
Penyebab : autoimmun
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Target Antigen biasanya tidak diketahui
Pada beberapa kasus: Target serangan imun
gangliosida (GM1, GQ1b)
Faktor presipitasi:
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Infeksi virus (HIV, CMV, varicella zoster)
Infeksi bakteri (campylobacter jenjuni, typhoid,
paratyphoid)
Immunisasi
Sistemik (Hodgkins disease, leukemia, hipertiroidisme,
sarkoidosis)
Transplantasi organ, operasi, kehamilan
Latar belakang GBS
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Epidemiologi GBS
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1- 4 kasus/100.000
Paling banyak pada pria
Meningkat sesuai usia
Insidennya bervariasi sesuai musim
Gambaran klinis GBS
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Gangguan Motorik:
paralisis yang progressif, simetris pada extremitas
bawah dan atas, bersifat asendern
dimulai dari distal ke proksimal
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Gangguan sensibilitas: Stocking, dan glove
sensory loss (dysesthesia)
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Gangguan otonom:
penyebab kematian
Clinical Picture of Polyneuropahty
(Valenstein, 2000)
Gambaran klinis GBS
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Atypical presentations
 Miller-Fisher
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Syndrome
Areflexia
Ophthalmoplegia
Ataxia
diagnosis GBS
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Riwayat penyakit sebelumnya atau vaksinasi
Dari pemeriksaan fisik (Physical Exam)
Laboratoratorium:
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Peningkatan kadar protein pada pemeriksaan LCS dan
rendahnya jumlah sel di LCS (disosiasi sitoalbumin)
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Electromyography – adanya blok konduksi saraf
KRITERIA GBS MENURUT GILROY DAN MEYER (1979)
1. Paralisis flasid simetris, difus
2. Gejala sensoris subyektif
3. Penyembuhan sempurna dalam 6 bulan
4. Disosiasi citoalbumin
5. Tanpa atau sedikit demam saat muncul paralysis
6. AL normal atau lymphositosis dengan sedikit atau tanpa
kenaikan KED.
Harus memenuhi 5 kriteria dari 6 kriteria
Pengobatan GBS
Fase akut
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Supportive care : monitoring fungsi vital
(perawatn ICU)
Pemberian IV imunoglobulin (ivIg) 400 mg/kg
selama 5 hari, plasmapheresis 40-50 ml/kg
plasma exchange diberikan 4 kali seminggu
Kortikosteroid
Artificial ventilation (if necessary)  paralysis
diafragma
Setelah fese akut
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Program rehabilitasi, bladder training, perbaikan
ADL (activity daily living)
Summary of nerve disorders
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Root
Disk, Herpes zoster
Plexus
Autoimmune, trauma,
neoplasm
Mononeuropathy
Trauma, entrapment
Multiple
mononeuropathy
Vasculitis...
Polyneuropathy Toxic, metabolic, nutritional
Polyradiculoneuropathy
Autoimmune
Neuromuscular junction
Disorders of the neuromusuclar
junction
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Release of acetyl choline:
Botulism (toxin = endopeptidase targeting
various proteins mediating exocytosis)
 Lambert-Eaton myasthenic syndrome
(antibodies to voltage-gated calcium channel)
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Acetylcholine receptor blockade:
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Myasthenia gravis (antibodies to ACh
receptor)
Myasthenia Gravis
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Kelemahan yang berfluktuasi
Mata: ptosis, diplopia
Bulbar weakness: dysarthria,
dysphagia
Kelemahan otot proksimal
Kelemahan respirasi
Normal reflexes
Normal sensation
Berkaitan dg thymoma
Berkaitan dg penyakit
autoimun
Penyakit autoimun pada transmisi
neuromuskular junction yang
diakibatkan oleh antibodi yang
menyerang reseptor asetilkolin atau
melawan muscle spesific receptor
tyrosine kinase
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Myasthenia gravis is a neuromuscular disease leading
to fluctuating muscle weakness and fatiguability.
It is an autoimmune disorder, in which weakness is
caused by circulating antibodies that block acetylcholine
receptors at the post-synaptic neuromuscular junction,
inhibiting the stimulative effect of the neurotransmitter
acetylcholine.
Myasthenia is treated medically with cholinesterase
inhibitors or immunosuppressants, and, in selected
cases, thymectomy.
At 200–400 cases per million it is one of the less
common autoimmune disorders.
Muscles become progressively weaker
during periods of activity and improve after
periods of rest. Muscles that control eye
and eyelid movement,
 facial expression, chewing, talking, and
swallowing are especially susceptible. The
muscles that control breathing and neck
and limb movements can also be affected
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Myasthenia Gravis
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Terapi:
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Acetyl cholinesterase inhibitors : pyridostigmin bromida 3x 60
mg
Plasmapharesis : plasma exchange
Imunoglobulin IV
Immunosupresan (kontroversi)
 Steroid : mulai 12-50 mg
 Azathioprine : 50 mg/hari
 Cyclosporine : awal 3-4 mg/kg/hari dalam dosis terbagi
 Cyclophosphamide : dosis 1-2 mg/kg/ hari
Thymectomy , indikasi:
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Timoma
Generalized myastenia yang tidak terkontrol dengan
antikolinesterase (< 50 th, 6-12 bulan tidak ada remisi spontan)
Krisis Mistenia
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Adalah keadaan eksaserbasi penyakit
Mistenia gravis dimana kelumpuhan
menyebabkan episode akut kegagalan
pernafasan
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Terjadi pada 74% setelah 2 tahun
miastenia gravis
Krisis Mistenia
Faktor pencetus :
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Infeksi, terutama infeksi saluran nafas
Pemakaian obat2an: aminoglikosid,
ciprofloksasin, klindamisin, propanolol, fenitoin
Tidak diketahui (30-40%)
Krisis Mistenia
Terapi :
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Kontrol airways, dan perbaiki ventilasi (jika perlu
menggunakan ventilator)
Terapi antikolinesterase
Kortikosteroid
Plasma axchange atau IV Ig
Penyakit otot (myopathy)
Symmetrical proximal weakness
 Reflexes normal (sometimes depressed)
 No sensory loss
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Myopathy (cont’d)
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Inherited
Dystrophies
 Congenital myopathies
 Channelopathies
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Acquired
endocrine
 inflammatory, including
autoimmune
 toxic (drugs...)
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Inflammatory myopathies
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Polymyositis
isolated
 with collagen vascular
disease
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Dermatomyositis
childhood
 adult: association with
cancer
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others
Dystrophy Musculorum
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Muscular dystrophy is a genetic condition
causing muscle weakness
Dermatomyositis - Polymyositis
KRITERIA DIAGNOSIS
Kelemahan otot-otot proksimal simetris
Rash tipikal pada dermatomyositis
Peningkatan enzim otot / plasma muscle enzymes (CK, aldolase, AST),
khususnya creatine kinase
Terdapat korelasi antara beratnya kelemahan dengan peningkatan enzim
Gambaran myopati pada pemeriksaan needle EMG
Gambaran abnormalitas yang khas pada biopsi otot (nekrosis serabut otot
dan degenerasi, dengan infiltrasi sel-sel inflamasi)
Polymyositis
Polymyositis is a disease of muscle
featuring inflammation of the muscle fibers
 The cause of the disease is not known
 Polymyositis is slightly more common in
females. It affects all age groups, although
its onset is most common in middle
childhood and in the 20s
 Weakness of muscles is the most common
symptom of polymyositis
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Amyotrophic lateral sclerosis
Lou Gehrig's disease
 Amyotrophic lateral sclerosis (ALS) is a
nervous system disease that attacks nerve
cells called neurons in your brain and
spinal cord
 The cause of ALS is not known
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Amyotrophic lateral sclerosis
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The disease belongs to a group of disorders
known as motor neuron diseases, which are
characterized by the gradual degeneration and
death of motor neurons.
In ALS, both the upper motor neurons and the
lower motor neurons degenerate or die, ceasing
to send messages to muscles
At first, this causes mild muscle problems. Some
people notice
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Trouble walking or running
Trouble writing
Speech problems
Multiple sclerosis
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Multiple sclerosis (MS) is a nervous system disease that
affects your brain and spinal cord. It damages the myelin
sheath
No one knows what causes MS. However, viral and
autoimmune etiologies have been hypothesized. It may
be an autoimmune disease
The symptom can include :
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Visual disturbances
Muscle weakness
Trouble with coordination and balance
Sensations such as numbness, prickling, or "pins and needles"
Thinking and memory problems
Key clinical features used to localize a neuromuscular disorder
Myopathy
•predilection for neck, limb girdle and proximal muscles
•occasional respiratory muscle involvement
•possible risk of myoglobulinuria
•no sensory loss
•normal tendon reflexes (early stage)
Neuromuscular junction
•cranial, limb girdle and proximal muscles
•may affect respiratory muscles
•no sensory loss
•autonomic symptoms present if pre-synaptic
•fatigueability when post-synaptic, post-exercise increase in strength when pre-synaptic
Neuropathy
•weakness and sensory signs
•may have associated autonomic signs
•may involve cranial nerves
•tendon reflexes decreased or absent
Motor neuron
•predominantly motor signs
•occasional sensory symptoms
•often asymmetric
•tendon reflexes may be increased if amyotrophic lateral sclerosis