Current Case: Spring 2019

Contributed by Samuel Ming Hin Lee, MD, PhD and Ioannis Karakis, MD, PhD, MSc
Emory University School of Medicine

Clinical Presentation

48 year old woman presented with multiple complaints including insomnia and bilateral hand cramps for several months followed by recent onset of progressively worsening generalized body cramps and muscle twitching. Associated symptoms included tingling in the toes bilaterally, generalized weakness, itching, and uncontrollable sweating. On examination, she had myokymia at orbicularis oculi, abductor pollicis brevis, and quadriceps bilaterally. Motor examination was significant for symmetrical weakness with bilateral arm abduction (MRC grade 5-) and hip flexors (grade 5-) but otherwise full strength except unable to fully test hand musculature due to pain and cramps. Sensation was normal in all limbs to multiple modalities. Motor nerve conduction studies (NCSs) of the left upper and lower extremities demonstrating stimulus induced after-discharges are shown below (arrows). Needle electromyography (EMG) in the first dorsal interosseous muscle demonstrated high-frequency (150-250 Hz), decrementing, repetitive spontaneous discharges of single motor units

Question 1: What is the most likely diagnosis?

  1. Cramp fasciculation syndrome
  2. Myotonic dystrophy
  3. Stiff person syndrome
  4. Satoyoshi syndrome
  5. Morvan syndrome
Answer: (click here)

A1: Correct answer: E. Morvan syndrome

Morvan syndrome was described in 1890 as a rare constellation of peripheral nerve hyperexcitability, dysautonomia, and encephalopathy with marked insomnia [2, 8].  Common symptoms include neuropathic pain, sensorimotor neuropathy, muscle twitching and/or muscle cramps, autonomic dysfunction including hyperhidrosis, skin itching, insomnia, neuropsychiatric symptoms and seizures [2, 8]. When symptoms are isolated in the peripheral nervous system, it is known as Isaac syndrome [1].

Cramp fasciculation syndrome is a peripheral nerve hyperexcitability disorder characterized by persistent muscle cramping and twitching in otherwise healthy individuals [1]. Myotonic dystrophy is a group of inherited muscular dystrophies characterized by weakness and inability to relax contracted muscles [1]. Stiff person syndrome is characterized by fluctuating muscle rigidity in the trunk and limbs and a heightened sensitivity to external stimuli [1]. Satoyoshi syndrome is characterized by painful muscle cramps, alopecia, diarrhea, and endocrinopathies [1].

Question 2: Which of the following autoantibody is responsible for this clinical presentation?

  1. Anti-voltage-gated calcium channel antibody
  2. Anti-voltage-gated potassium channel complex antibodies
  3. Anti-glutamic acid decarboxylase 65 antibody
  4. Anti-ganglionic acetylcholine receptor antibody
Answer: (click here)

A2: Correct answer: B. Anti-voltage-gated potassium channel complex antibodies

Morvan syndrome is associated with antibodies to voltage-gated potassium channels including LGI1 and CASPR2 [5, 8]. A substantial portion of Morvan syndrome cases are paraneoplastic, with the most common cancer being thymomas [2, 3, 8]. After this patient was diagnosed with Morvan syndrome, she received 5 doses of high-dose methylprednisolone followed by a course of IVIG with improvement in all of her symptoms. However, CT and MRI of the chest, abdomen and pelvis failed to identify any malignancy.

Anti-voltage-gated calcium channel antibody is seen in Lambert Eaton myasthenic syndrome [7]. Anti-glutamic acid decarboxylase 65 antibody is associated with stiff person syndrome, limbic and brainstem encephalitis, ophthalmoplegia, and movement disorders such as ataxia and parkinsonism [7]. Anti-ganglionic acetylcholine receptor antibody is associated with peripheral neuropathy, dysautonomia, and encephalopathy, but not associated with muscle twitching, insomnia, neuropsychiatric symptoms and seizures [4].  

Question 3: The after-discharges observed on motor NCSs can be seen in which of the following?

  1. Isaac syndrome
  2. Myotonia congenita
  3. Paramyotonia congenita
  4. Hyperkalemic periodic paralysis
  5. Rattle snake envenomation
  6. Organophosphate poisoning
  7. All of the above
Answer: (click here)

A3: Correct answer: G. All of the above

Prolonged after-discharges can be seen in motor NCSs supportive of nerve hyperexcitability which can be seen in neuromyotonia [3, 5]. However, after-discharges has been reported in a variety of conditions, including myotonia congenita, paramyotonia congenita, hyperkalemic periodic paralysis, rattle snake venom poisoning, and organophosphate poisoning [1].

Question 4: The description of needle EMG findings is best described as:

  1. Myotonia
  2. Fasciculations
  3. Neuromyotonia
  4. Complex repetitive discharges
Answer: (click here)

A4: Correct answer: C. Neuromyotonia

EMG shows neuromyotonic discharges which are high-frequency (150-250 Hz), decrementing, repetitive spontaneous discharges of single motor units [2, 8]. Fasciculations are irregular single spontaneous discharges of single motor units [6]. Myotonic discharges are high-frequency (20-150 Hz), incrementing and decrementing, repetitive spontaneous discharges of muscle fibers [6].  Complex repetitive discharges are bursts of regular high-frequency spontaneous discharges (5-100 Hz) of multiple muscle fibers time-linked together [6].

References

  1. Amato AA, Russell JA (2008) Neuromuscular disorders. McGraw-Hill Medical, City
  2. Irani SR, Pettingill P, Kleopa KA, Schiza N, Waters P, Mazia C, Zuliani L, Watanabe O, Lang B, Buckley Cet al (2012) Morvan syndrome: clinical and serological observations in 29 cases. Ann Neurol 72: 241-255 Doi 10.1002/ana.23577
  3. Lukas RV, Rezania K, Malec M, Salgia R (2013) Teaching Video NeuroImages: myokymia and nerve hyperexcitability as components of Morvan syndrome due to malignant thymoma. Neurology 80: e55 Doi 10.1212/WNL.0b013e31827f0fa1
  4. McKeon A, Lennon VA, Lachance DH, Fealey RD, Pittock SJ (2009) Ganglionic acetylcholine receptor autoantibody: oncological, neurological, and serological accompaniments. Arch Neurol 66: 735-741 Doi 10.1001/archneurol.2009.78
  5. Niu J, Guan H, Cui L, Guan Y, Liu M (2017) Afterdischarges following M waves in patients with voltage-gated potassium channels antibodies. Clin Neurophysiol Pract 2: 72-75 Doi 10.1016/j.cnp.2017.02.002
  6. Preston DC, Shapiro BE (2013) Electromyography and neuromuscular disorders : clinical-electrophysiologic correlations. Elsevier Saunders, City
  7. Tobin WO, Pittock SJ (2017) Autoimmune Neurology of the Central Nervous System. Continuum (Minneap Minn) 23: 627-653 Doi 10.1212/CON.0000000000000487
  8. Vincent A, Pettingill P, Pettingill R, Lang B, Birch R, Waters P, Irani SR, Buckley C, Watanabe O, Arimura Ket al (2018) Association of Leucine-Rich Glioma Inactivated Protein 1, Contactin-Associated Protein 2, and Contactin 2 Antibodies With Clinical Features and Patient-Reported Pain in Acquired Neuromyotonia. JAMA Neurol:  Doi 10.1001/jamaneurol.2018.2681