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B. Jane Distad, MDAssociate Professor

Department of Neurology2015

Amyotrophic lateral sclerosis Nerve conduction studies/Electromyography Differential diagnosis Other motor neuron syndromes

Spinal muscular atrophy Poliomyelitis

Prevalence 2 to 7 per 100,000 Incidence 1.4 per 100,000 Male: female ~1.6:1 Forms/presentations

Classic amyotrophic lateral sclerosis Progressive bulbar palsy progressive muscular atrophy primary lateral sclerosis <1/2 of pure PLS maintain diagnosis @ mean 8 years*

*Gordon PH, March 2006

10% of all ALS SOD1 15-20% C9ORF72 40%

hexanucleotide repeat expansion in noncoding gene region

associated with FTD and TDP-43 inclusions

TARDP 1-4% FUS 1-5%

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Upper motor neuron (UMN) Lower motor neuron (LMN) Bulbar CN 9, 10 , 12 most Respiratory

Weakness Increased tone Increased deep

tendon reflexes Reduced speed of

fine motor movements Finger taps in 10 sec Foot taps in 10 sec

Pseudobulbar signs

http://www.bing.com/images/search?q=upper+and+lower+motor+neuron+pathology&qs=n&form=QBIR&pq=upper+and+lower+motor+neuron+pathology&sc=0-0&sp=-1&sk=#view=detail&id=D53E380ECBD1C165021BE430EC122E9955E6907D&selectedIndex=1

Weakness Atrophy Fasciculations Cramps Decreased deep

tendon reflexes

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http://www.google.com/imgres?q=amyotrophic+lateral+sclerosis+and+tongueatrophy&um=1&hl=en&rlz=1I7DMUS_en&biw=1280&bih=857&tbm=isch&tbnid=jKawukTErsvXEM:&imgrefurl=http://www.sharinginhealth.ca/conditions_and_diseases/als.html&docid=uFdJs9lIiNuhdM&imgurl=http://www.sharinginhealth.ca/images/ALStongue1.jpg&w=500&h=385&ei

=P2hdT4CbJ-iniQKv-qmUCw&zoom=1&iact=hc&vpx=450&vpy=188&dur=266&hovh=197&hovw=256&tx=157&ty=90&sig=113904820317176700556&page=1&tbnh=135&tbnw=181&start=0&ndsp=26&v

ed=1t:429,r:2,s:0

http://www.google.com/imgres?q=ALS+and+hand+atrophy&um=1&hl=en&rlz=1I7DMUS_en&biw=1280&bih=857&tbm=isch&tbnid=ZWRrWHOMHyBjkM:&imgrefurl=http://www.tummytuckformen.com/hand_finger_muscle_atrophy_from_ulnar_nerve_damage.html&docid=qL_QqqnxVfiFHM&itg=1&imgurl=http://www.tummytuckformen.com/images/

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:429,r:25,s:20

Creatine kinase (CK) – elevated in 50% of patients to 2-3 x normal UW lab normal value 30–285 mg/dL 2-3 x normal = 570-855

Involves select degeneration of motor cells in spinal cord, brainstem and to a lesser extent, cortex

PathologyDegeneration of

anterior horn cells results in denervation of

muscle fibers

Collateral sprouts from surviving motor neurons re-innervate

the affected motor units

Denervation atrophy with fiber type

grouping

Clinical diagnosis- In the absence of a biological marker to establish

diagnosis, electrodiagnostics (EDX) play a critical role in the establishing the diagnosis and severity

NCS/EMG Supports lower motor neuron component Excludes other etiologies SUCH AS?

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Ulnar motor Recording ADM Stimulation up to axilla +/- Erb’s point

Peroneal motor Recording EDB Stimulation to knee

Sensory nerve action potentials: ulnar and sural Late responses – F waves Contralateral studies in those with upper

motor neuron signs lacking

Compound muscle action potentials- normal or reduced amplitude

Normal or only slightly reduced speed Minimal “demyelinating” features

Prolonged distal latencies (<125% ULN)

Reduced conduction velocities (>80% LLN)

Prolonged F wave latencies (<125% ULN)

Normal sensory nerve studies

Fibrillation potentials and positive sharp waves widespread – diffuse denervation

Fasciculation potentials motor neuron irritability in this setting,

but non-specific Large and small fibrillation potentials

recent and chronic denervation

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Awaji Criteria for the Diagnosis of Amyotrophic Lateral Sclerosis: A

Systematic ReviewJoão Costa, MD, PhD; Michael Swash, MD; Mamede de Carvalho, MD, PhD Arch Neurol. 2012;69(11):1410-1416.

doi:10.1001/archneurol.2012.254.

EMG CRITERIA

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https://www.youtube.com/watch?v=i1Ofx7d0eBg

http://youtu.be/i1Ofx7d0eB

FASCICULATION POTENTIALS IN AMYOTROPHIC LATERAL SCLEROSIS AND THE DIAGNOSTIC YIELD OF THE AWAJI ALGORITHM. MANA HIGASHIHARA, MASAHIRO SONOO, ICHIRO IMAFUKU, et al Muscle Nerve 45: 175–182, 2012

Limb – 3 limbs Proximal and distal muscles Muscles with different nerve innervation Muscles with different root innervation

exclude structural pathology – i.e., severe cervical/lumbar spondylosis as etiology Thoracic (or abdominal) Cranial nerve-innervated

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Thoracic paraspinal muscles 2-3 segments Avoid T11-12 Abnormal in 78%

Craniobulbar* one pathological EMG finding in (91.7%) with both

frontalis and orbicularis oris together. 83.3% for frontalis alone 75% orbicularis oris alone

Finsterer J, Erdorf M, Mamoli B, Fuglsang-Frederiksen A. Needle electromyography of bulbar muscles in patients with amyotrophic lateral sclerosis: evidence of subclinical involvement. Neurology. 1998 Nov;51(5):1417-22. PubMed PMID: 9818871

Bulbar At least one Tongue, masseter,

sternocleidomastoid, facial muscles, (trap)

Shorter duration MUAPs

Higher firing frequency

Reduced in number Recruit poorly Rapid discharge Reduced interference pattern Large amplitude Polyphasic

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3/4 regions involved Bulbar Cervical Thoracic Lumbosacral

Active – positive sharp waves Fibrillation and fasciculation potentials,

Chronic – Reduced number MUAPs increased amplitude/duration motor unit action

potentials (MUAPs)

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Progressively stronger electrical shocks to nerve result in stepwise increase in amplitude of evoked compound muscle action potential (CMAP)

Each addition = recruitment of one motor unit Ratio between full response from max

stimulation to average increment Noninvasive Mean number differs per muscle eg, 200 for

EDB, 250 or 340 for thenar muscles

Asymmetric Multifocal Involves – active and chronic

more than 2 muscles innervated by different nerves and different spinal roots in at least 3 limbs (or 2 limbs and cranial)

Rarely Lead intoxication [Chronic mercurialism] Multifocal motor neuropathy * MAMA Lower motor neuron only – hexosaminidase deficiency – autosomal recessive Immune-mediated disease such as multifocal acquired

motor axonopathy (MAMA) Cervical spondylosis ** Inclusion body myositis ***

Rarely Lead intoxication [Chronic mercurialism] Multifocal motor neuropathy *conduction block Lower motor neuron only – hexosaminidase deficiency – autosomal recessive Immune-mediated disease such as multifocal acquired

motor axonopathy (MAMA)

Cervical spondylosis ** Inclusion body myositis ***

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Rarely Lead intoxication [Chronic mercurialism] Multifocal motor neuropathy *conduction block MAMA Lower motor neuron only – hexosaminidase deficiency – autosomal recessive Immune-mediated disease such as multifocal acquired

motor axonopathy (MAMA) Cervical spondylosis *root only Inclusion body myositis *

Rarely Lead intoxication [Chronic mercurialism] Multifocal motor neuropathy *conduction block MAMA Lower motor neuron only – hexosaminidase deficiency – autosomal recessive Immune-mediated disease such as multifocal acquired

motor axonopathy (MAMA) Cervical spondylosis *root only Inclusion body myositis *myopathic units

Slowly progressive Begins distally Fasciculation/cramp

uncommon <45 years Male:female 2:1 More nerve than neuron

distribution Weakness>atrophy Normal to decreased

DTRs

Partial conduction block

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Most common presentation – one hand first Fasciculations clinically and

electrophysiologically Start in affected area Include bulbar (eg genioglossus if

symptomatic) Include thoracic paraspinals

CRDs unusual – seen with more chronic process

Myotomal – should not spare individual nerves in the same myotome Eg, if C8 innervated median muscle is abnormal, a

C8 innervated ulnar muscle should also be abnormal Chronic myopathies, particularly inclusion

body myositis active denervation with long-duration, high-

amplitude polyphasic MUAPs, but recruitment is usually normal or early

Decreased activation may be seen secondary to upper motor neuron dysfunction

“On the whole, the EMG picture of classic ALS is one of” Partial denervation, reinnervation, decreased activation and decreased

recruitment of MUAPs in multiple muscles innervated by different

nerves and myotomes

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prevalence of 1 in 6000 live born infants Majority inherited – Recessive linked to locus 5q13 in > 95% of patients Werdnig-Hoffman – most severe resulting in

death in 2 years Kugelberg-Welander

Adolescent or adult onset Slowly progressive Symmetrical proximal weakness Lack bulbar and long-tract signs Positive family history DNA analysis – survival motor neuron

Kennedy’s disease Onset 3rd-5th decade X-linked, some sporadic Muscle cramps with exercise Proximal muscles then bulbar Distal muscles affected later

Rest or contraction fasciculations of face, chin Reflexes hypoactive Gynecomastia in most Diabetes, infertility Mild CK elevation Expansion of a trinucleotide repeat (CAG) on

androgen receptor gene NCS/EMG – chronic denervation >

Nerve conduction studies Normal sensory studies; motor latencies & CV Reduced amplitude compound muscle action

potentials EMG

Spontaneous activity Ongoing denervation Chronic reinnervation Fibrillation and fasciculation potentials not prominent

Motor unit action potentials High amplitude, long duration motor unit action potentials Reduced recruitment

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Nerve Latency Amplitude CV F wave lat Temp.(C)

Peroneal 4.8 3.6/3.2/3.2 42/53 44.9 32.0

Tibial 5.0 15.9/ 14.9 50 46.9 32.1

Median 3.7 0.7/0.5 43 31.2

Ulnar R NR

Ulnar L 2.8 6.9/6.8/6.3 60/59 24.3

Sural 2.7 21 50 31.4

Median S 2.9 60 48 31.3

Ulnar S 2.9 50 48 31.7

Muscle and side Fibs Fasci Poly Amp (mV) Dur (ms) Recruitment Comm

Tibialis anterior.R/L trc - - .6-2 7-14 Normal

Gastrocnemius (Med).R/L 2+ 1+ Rare . INC+ 7-14 Mild reduced dc rlx

Vastus lateralis.R - - - .6-2.5 7-14 Mild reduced insrtl

Hamstring (lat).R - - - .6-1.6 INC Very reduced pain

Vastus medialis.L - - - .6-2 7-12 Mild reduced

1st dorsal interosseous.R 4+ 1+ INC INC Very reduced

Pronator teres.R 2+ 1+ Rare . INC INC Mod reduced

Extensor digitorum com.R 3+ 1+ - .6-2.2 7-14 Mod reduced

Biceps brachii.R/L - - - .6-2.2 7-12 Mild reduced

Triceps brachii.R 2+ 1+ Few .6-2.2 INC Mild reduced

1st dorsal interosseous.L 1+ - - . INC INC Mild reduced hfdc

Extensor digitorum com.L - - - .6-2 7-14 Mild reduced hfdc

Pronator teres.L - - - .6-1.6 7-12 Normal

Genioglossus.L ? - - .6-1.6 7-12 Mild reduced No rlx

Lumbar paraspinals.R 1+ -

Thoracic paraspinals.R 2+ - t9

Cervical paraspinals R ? ? no rlx

YES – ALS! Gordon PH, Cheng B, Katz IB, Pinto M, Hays AP, Mitsumoto H, Rowland LP. The natural history of primary lateral sclerosis. Neurology. 2006 Mar 14;66(5):647-53.

Kimura J. Electrodiagnosis in disease of nerve and muscle: Principles and Practice, Ed 2. F. A. Davis Company, Philadelphia, 1989

Murray B, Mitsumoto H. Amyotrophic lateral sclerosis. In Katirji B, Kaminski HJ, Preston DC, Ruff RL, Shapiro BE (ed). Neuromuscular disorders in clinical practice. Butterworth-Heinemann, Boston, 2002.

Preston DC, Shapiro BE. Electromyography and neuromuscular disorders. Butterworth-Heinemann, Boston, 1998.

Williams DB, Windebank, AJ. Motor neuron disease. In Dyck PJ, Thomas PK (ed). Peripheral neuropathy 3rd edition. Philadelphia, Saunders, 1993, 1028-50.

Sinan Bir L, Acar G, Kilincer A. EMG findings of facial muscles in ALS. Clin Neurophysiol. 2006 Feb;117(2):476-478.

de Carvalho M, Dengler R, Eisen A, et al, Review Electrodiagnosticcriteria for diagnosis of ALS. Clinical Neurophysiology 119 (2008) 497–503.