EMG Blind Spots: What Your Study Can Miss

Disorders of the NMJ

W. David Arnold, MDAAPMR 2014

Outline

• Review of Prototypical NMJ Disorder, Myasthenia Gravis, and the General Approach to NMJ Disorders

• Review a series of 4 Cases to Highlight Potential Pitfalls and Key Concepts in NMJ Edx studies

Case 1: “Proximal Limb Weakness”

• 18 year old woman presents with a progressive proximal limb weakness is sent to the EMG Lab

Limb Girdle Muscular Dystrophy?

• Examination:– 4 grade proximal limb weakness– Normal bulbar strength, sensation, and

reflexes

Case 1: NCS and EMG

• Normal median sensory and motor response

• EMG: short duration, small amplitude motor unit action potentials with early recruitment without fibrillations

Case 1: Proximal Limb Weakness (Cont.)

• EMG and NCS: Non-irritable myopathy

• Diagnostic consideration was given to a possible limb girdle muscular dystrophy

• Muscle Biopsy: normal • Thoughts?

Case 1: Additional Studies

• Repetitive ulnar nerve stimulation at 3 Hz

~50% decrement• SFEMGIncreased jitter and blocking

Follow up

Lab testing:– Elevated acetylcholine receptor

antibodies

Diagnosis: acetylocholine receptor antibody positive myasthenia gravis (MG)

Treatment: Excellent response to pyridostigmine and immunomodulatory treatments

338 charts of patients with NMJ disorders

6 patients underwent muscle biopsy for possible myopathy

2 with coexistent inflammatory muscle dz

4 with NMJ disorders mimicking myopathy (based on normal muscle bx)

Consider RNS in patients with weakness

Clinical Pearl of Case 1:

Ask the Correct Question

MG

• MG is the most common NMJ disorder• Prevalence of 20 in 100,000 and incidence

of 2 per 100,000. (Phillips Ann N Y Acad Sci. 2003)

• Antibodies– Ach receptor antibodies (80%)– Muscle specific tyrosine kinase (MuSK) (10%)– Antibody negative (5%-10%)

• Treated with cholinesterase inhibitors and immunomodulatory treatments

NMJ Disorders: History• Weakness: proximal muscles with fatigability

– Severity of involvement: Ocular>bulbar>limb>respiratory

• Sensory: No sensory loss, paresthesia, or neuropathic pain

• Autonomic: dry mouth, blurry vision, impotence, constipation, and difficulty with urination– Some disorders such as Lambert Eaton

myasthenic syndrome (LEMS) and botulism

Generalized fatigue ≠ NMJ disorder

NMJ Disorders: Examination • Weakness in proximal limb, ocular, and

bulbar muscles– Distal or focal weakness may occur in

12% of MG (Wirtz et al 2002)

– Extraocular and bulbar weakness are early and prominent in MG and botulism

– Less prominent extraocular weakness in LEMS

• Reflexes are normal in postsynaptic disorders such as myasthenia gravis but characteristically absent or reduced in presynaptic NMJ d/o

• Sensory function is normal• Pupillary responses are usually reduced

in botulism

Post-synaptic NMJ disorders• Sensory NCS

-normal• Motor NCS

-usually normal CMAP amplitude

• EMG-Possibly short duration, low amplitude, unstable MUAP’s if severe (Jiggle)

• Slow RNS (3 Hz)-decrement

(60-80% of generalized MG)

• CMAP with 10 sec exercise(or Rapid RNS, 20-50 Hz)

-no increment• CMAP with Exercise

-no increment• SFEMG

-Jitter and blocking (95-98% MG)

(Nl jitter in weak muscle ≠ MG)

Post-synaptic NMJ disorder

Pre-synaptic NMJ disorderSensory NCS

-normalMotor NCS

-usually low CMAP amplitude

EMG-Possibly short duration, low amplitude, unstable MUAP’s if severe-some disorders with fibrillations (botulism)

Slow RNS (3 Hz)-decrement

CMAP with 10 sec exercise(or Rapid RNS, 20-50 Hz)

-increment 300% in one muscle or 100% in

three (diagnostic for Lambert Eaton MS)

SFEMG-Jitter and blocking

(jitter and blocking decrease with increasing firing rate)

Presynaptic NMJ

Pre-exercise

Post-exercise

350% increment following 10 seconds exercise

Case 2: Dysarthria• 64 year old woman with symptoms of

progressive dysarthria and facial weakness is sent to the EMG Lab

Possible myasthenia gravis?• Examination

– Mild facial and moderate tongue weakness– Tongue fasciculations– Normal limb strength– Generalized Brisk reflexes and jaw jerk

Case 2: Nerve Conduction Studies

Median and ulnar sensory responses are normalMedian and ulnar motor responses are normalRepetitive nerve stimulation at 3 Hz

-Orbicularis Oris with >20% decrementMyasthenia

Gravis?

Case 2: Electromyography

Single Fiber EMG-Increased jitter and blocking in frontalis and extensor digitorum

EMGFibrillations/fasciculations/dec recruitment/enlarged motor unit action potentials (mentalis and tongue)Limb muscles normal

Jitter and Blocking

Example: Post-synaptic NMJ disorder

Case 2

Clinical Pearl of Case 2:

Not all that Jitters is Myasthenia

the “False Positive” testAmyotrophic Lateral Sclerosis & NMJ transmission defect• Severe decrement frequently seen on RNS (reported up

to 35% of CMAP amplitude) (I have seen up to 50%)• Increased decrement correlates with faster progression

and worse prognosis Daube 2004; Wang 2001

• SFEMG: increased jitter and block may be early finding, prior to denervation (also seen in early reinnervation)

• Axonal Stimulation SFEMG: lack of facilitation with increasing frequency of stimulation

Arimura 1995

Case 3: Seronegative MG

A 58 year old woman with a 30 year history of seronegative myasthenia gravis

PMH: poliomyelitis at age 6 requiring ventilation support in an iron lung for a month

PE: normal CN exam, severe proximal limb weakness with fatigability, normal sensation and reflexes

Case 3: Seronegative MG

• 3Hz RNS with up to 70% decrement in proximal muscles

• She describes dramatic improvement with pyridostigmine

• Worsening with prednisone

• No improvement with IVIG or PLEX

• Ideas?

Clinical Pearl of Case 3:Hoof beats (aka decrement)? Don’t assume

it is a horse (MG)

– Multiple NMJ disorders may fall within this clinical presentation• Seronegative (autoimmune) MG• Congenital Myasthenic syndromes• Other neuromuscular disorders with

secondary NMJ effects or clinical patterns similar to NMJ disorders

Congenital Myasthenic Syndrome

• Historical points in case 3 suggesting this possibility:– No clear response to

immunomodulation– Atypical phenotype

(Severe disease with minimal to no bulbar involvement)

– PMH of “polio” after which she states she was “normal” in every way until developing weakness in her 20’s

– On more direct questions she described being a “blue baby” at birth

• Electrodiagnosis of CMS

Case 4: MG second opinion

45 year old man with progressive ptosis, dysphagiaFH: mother with “seronegative myasthenia gravis”Examination: bilateral ptosis and extraocular muscle weakness without clear fatigability; mild proximal limb weakness

Antibody testing: AChR and MuSK Antibodies (-)

EMG and NCS: decrement on repetitive nerve stimulation studiesDiagnosed with seronegative myasthenia gravis but then had minimal response to immune therapies and pyridostigmine?

Ideas?

Case 4: Repeat EMG and NCS

• NCS: multiple mononeuropathies c/w the patient’s known HNPP

• RNS: normal• SFEMG: mildly increased jitter in

frontalis with no blocking• EMG: Short duration small

amplitude motor unit action potentials with sparse fibrillations in proximal limb and facial muscles

Case 4: Pre and Post Surgery Images

Clinical Pearl of Case 4: When in doubt, trust your exam… double

check technique

Movement artifact is significant challenge in repetitive nerve stimulation and can lead to false positive tests

Our patient: • Lacked clinical features of fatigability or response to

treatment• Diagnosed with oculopharyngeal muscular dystrophy

(OPMD)– Autosomal dominant slowly progressive hereditary muscle disorder– GCG repeat expansion (8-13)– Often mistaken for seronegative MG– Typically later/less involvement of extraocular muscles

Thanks!

Questions?

William.arnold@osumc.edu

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