Summer 2021

Current Case: Summer 2021

Contributed by:
James D. Triplett B.Med and Ruple S. Laughlin, MD
Mayo Clinic Rochester

Case Presentation

A 79 year-old male with history of chronic lymphocytic leukemia (CLL) on irbutinib for 10 months presented for neuromuscular evaluation due to  an 8 month history of fatigue,  lower extremity weakness and occasional calf cramping. Further history revealed development of postural dizziness, >15 Lb weight loss and constipation over the last 6 months. Examination demonstrated mild weakness of left ankle inversion and iliopsoas bilaterally.  Sensory examination showed absent vibration sense at the toes and without deep tendon reflex abnormalities. Serological evaluations revealed a normal creatinine kinase of 40 (U/L) and low level N-type voltage gated calcium channel antibodies (0.09 nmol/L). Electrodiagnostic testing was recommended to further evaluate his symptoms.

Nerve conduction studies revealed normal amplitude compound muscle action potentials with reduced motor conduction velocities in the left upper and lower extremities. F-wave latencies were not prolonged compared to F-wave estimate. The median sensory nerve action potential (SNAP) was attenuated with prolonged distal sensory latency.  The sural and ulnar SNAPs were normal but the R1 blink latency was mildly prolonged.  2 hertz repetitive stimulation of the left fibular and ulnar nerves demonstrated neither decrement nor facilitation after brief exercise.

Needle electromyography (EMG) examination revealed early recruitment of mixed long and short duration polyphasic motor unit potentials with occasional fibrillation potentials in distal lower extremity muscles. Proximal upper and lower limb muscles revealed small, polyphasic, rapidly recruited motor unit potentials, not accompanied by fibrillation potentials or myotonic discharges.  Overall, needle EMG findings were most concerning for an underlying myopathy with the NCS findings suggesting some degree of overlying motor predominant neuropathy with predominantly demyelinating features as well as a left median neuropathy at the wrist.

Electrodiagnostic findings supported proceeding with muscle biopsy, which was performed of the right gluteus medius.  Pathology was consistent with systemic amyloidosis-associated myopathy. Amyloid subtyping showed this to be ATTR (transthyretin)-type amyloid deposition.

Figure 1: (A) Left median sensory nerve conduction study: distal sensory latency 4.3 msec (normal <3.6 msec), amplitude 11 mV (normal >15) mV, sensory conduction velocity 47 m/sec (Normal >56 m/sec) (10µV/Div, 1.5msec/Div); (B)  Left fibular motor nerve conduction study: distal motor latency 6.3 (normal <6.6), amplitude 2.3 mV ( normal >2 mV) conduction velocity 30 m/sec (normal >41 msec) (2mV/Div, 5msec/Div); (C)EMG left gluteus maximus revealing low amplitude, short duration motor unit potentials (200µV/Div, 50msec/Div); (D) EMG of left deltoid revealing low amplitude, short duration polyphasic motor unit potentials (200µV/Div, 50msec/Div)

 

Question 1: Is CK typically elevated in systemic amyloidosis-associated myopathy?:

  1. Yes
  2. No
Answer: (click here)

Correct answer: No.

Creatinine kinase is typically normal in systemic amyloid associated myopathies. In one series CK was modestly elevated (<2.5 upper limit of normal) in 11/38 patients with systemic amyloid associated myopathies (AL amyloid, ATTR amyloid, SSA and AGel amyloidosis). 1 Elevated CK levels >2.5 upper limit of normal are suggestive of either AL amyloidosis or isolated amyloid myopathies including anoctaminopathy-5 and dysferlinopathies.1

Question 2: The presence of median neuropathy at the wrist is rarely encountered in systemic amyloidosis:

  1. True
  2. False
Answer: (click here)

Correct answer: False.

Median neuropathy at the wrist is the presenting symptom in 16% of patients and is reported in 40% of all patients with AL and ATTR associated cardiac amyloidosis and in 5-18% of patients with systemic amyloidosis-associated myopathy.1-3 Median neuropathy at the wrist can be an important clue and often precedes the diagnosis of amyloid by years. 3,4

Amyloid deposition is identified in 10-20% of cases where histopathological analysis of tenosynovial biopsy performed during carpal tunnel release surgery of amyloid patients. 3 in comparison to identification of amyloid in 55-75% of patients who undergo abdominal fat pad biopsy.5 Clinical factors that should alert clinicians to request a histopathological analysis of tenosynovial biopsy include male age > 50, female age >60, bilateral median neuropathies at the wrist, biceps tendon rupture, spinal stenosis, a history of congestive cardiac failure or cardiac arrhythmias.3   

Question 3: The concentric needle examination finings in amyloid myopathy are similar to other chronic inflammatory myopathies?

  1. True
  2. False
Answer: (click here)

Correct answer: True.

The electrodiagnostic features of amyloid myopathy are typically that of a chronic myopathy with rapidly recruiting, short duration, polyphasic motor unit potentials seen in in the majority of muscles and mixed short and long duration polyphasic motor unit potentials seen in approximately 20% of muscles.1-2 Fibrillation potentials and positive sharp waves, which are thought to represent muscle fiber splitting, vacuolization or inclusions  are seen in the of patients with amyloid myopathy and in up to 70% of all muscles tested.1 Electrical myotonia is reported in a minority of cases.1

 

References

  1. Liewluck T, Milone M. Characterization of isolated amyloid myopathy. European Journal of Neurology. 2017; 24:1437-1445.
  2. Rubin DI, Hermann RC. Electrophysiologic findings in amyloid myopathy. Muscle Nerve. 1999; 22(3): 355-359.
  3. Donnelly JP, Hanna M, Sperry BW, et al. Carpal Tunnel Syndrome: A Potential Early, Red-Flag Sign of Amyloidosis. J Hand Surg Am. 2019;44(10):868-876.
  4. Bishop E, Brown EE, Fajardo J, et al. Seven factors predict a delayed diagnosis of cardiac amyloidosis. Amyloid. 2018;25(3): 174-719.
  5. Ansari-Lari MA, Ali SZ. Fine-needle aspiration of abdominal fat pad for amyloid detection: a clinically useful test? Diagn Cytopathol. 2004; 30(3): 178-81.

 

Last updated: October 21, 2021

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