Peripheral Nerve Hyperexcitability Syndromes (Peripheral Nerve and Motor Neuron Disorders 2017)

Educational Objectives

The goal of this program is to improve diagnosis and treatment of peripheral nerve and motor neuron disorders. After hearing and assimilating this program, the clinician will be better able to:

1. Diagnose peripheral nerve hyperexcitability syndromes.

Summary

Peripheral nerve hyperexcitability syndromes: Group of disorders that present with cramps, twitches, and stiffness of muscles; symptoms may be mild; patients have characteristic involuntary abnormal muscular activity.

Diagnosis: EMG — may not detect mildest type (cramp-fasciculation syndrome); most other syndromes characterized by continuous or frequent abnormal activity on EMG.

Cramp-fasciculation syndrome: Patients present with myalgia and cramps but no weakness; muscle twitches (predominantly in legs but sometimes in arms) commonly reported; causes no other disturbances and typically benign; to make diagnosis, fasciculation should be documented; some patients have antibodies to voltage-gated potassium channels (VGKC); EMG may identify fasciculations or abnormal discharges, such as myokymia; EMG occasionally negative if patient tested between episodes; as VGKC antibodies found only in minority of affected patients, etiology (ie, autoimmune versus genetic) uncertain; twitches and cramps respond to low doses of carbamazepine.

Isaacs syndrome: Also referred to as acquired neuromyotonia; patients have muscle stiffness, slow movements, and sometimes cramps; syndrome tends to be generalized, affecting arms and legs; in severe cases, patient may exhibit bradykinesia that resembles Parkinson syndrome; disease may start at any age; undulating movements of muscles often first symptom noted by patient; muscle twitches and stiffness do not disappear during sleep (this finding pathognomonic for Isaacs syndrome); syndrome may be mild to severe; patients with severe Isaacs syndrome significantly disabled and may have difficulty swallowing and slurred speech; few patients have dysautonomia with hyperhidrosis, drooling, or abdominal pain; mild forms may remain undiagnosed, and severe forms may be misdiagnosed; patients often have antibodies to VGKC; myokymia and neuromyotonia on EMG in combination with antibodies to VGKC strongly suggest Isaacs syndrome; antibodies typically directed to contactin associated proteinlike 2 (CASPR2).

Management: First-line treatment of Isaacs syndrome sodium channel blockers; patients with moderate or severe disease who have slowness of movement, frequent stiffness, or difficulty with ambulation may require additional therapies such as IV immunoglobulin (IVIg) or steroids.

Morvan syndrome: Overlaps with and may be difficult to distinguish from Isaacs syndrome; compared with patients with Isaacs syndrome, those with Morvan syndrome have more pronounced disorder of central nervous system (CNS) and autonomic findings; patients may have stiffness, muscle cramps, slow movements, myokymia, and visible muscle twitches; in addition, they have prominent dysautonomia that may be manifested as cardiac arrhythmia and sphincteric dysfunction; prominent central manifestations may include hallucinations, delirium, and severe sleep disturbances such as insomnia; they may resemble patients with encephalitis; Morvan probably less common than Isaacs syndrome, but both disorders rare.

Differential diagnosis: Several disorders originating in muscles or CNS are characterized by muscle stiffness and slowness of movement; clinician should first determine whether etiology of stiffness appears to be central; spasticity and spastic gait indicated by concomitant findings of hyperreflexia, pyramidal signs, and positive Babinski sign; occasionally, patients with stiffness have no upper motor neuron signs.

Stiff person syndrome: Most difficult disease to distinguish from peripheral nerve hyperexcitability syndromes (additional testing required to distinguish among these disorders); stiff person syndrome originates in CNS; syndrome causes stiffness and sometimes cramps and problems with gait; unlike Isaacs and Morvan syndromes, stiff person syndrome usually not associated with delirium, hallucinations, or dysautonomia; stiff person syndrome may be associated with epilepsy or diabetes mellitus; EMG usually does not show myokymia or myotonia; >70% of patients with stiff person syndrome have antibodies to glutamic acid decarboxylase (GAD); in patients with stiff person syndrome, stiffness disappears during sleep.

Other disorders in differential diagnosis: Among other disorders that produce stiffness, myotonias most common, especially nondystrophic myotonias as such as myotonia congenita; these disorders not associated with muscular weakness, but patients may exhibit stiffness and difficulty initiating movements; symptoms improve as patient moves; EMG shows prominent myotonia without myokymia or neuromyotonia.

Electromyography: Myokymia and neuromyotonia hallmarks of peripheral nerve hyperexcitability syndromes; neuromyotonia usually specific for these syndromes, but myokymia also seen in other disorders, such as radiation plexopathy, carpal tunnel syndrome, and Guillain-Barré syndrome; discharges seen in these disorders differ from those observed in patients with myotonic disorders (eg, myotonia congenita); inexperienced electromyographer may have difficulty distinguishing neuromyotonia from myotonia; myotonia tends to disappear as patient continues to move limb, but neuromyotonia remains unchanged; neuromyotonia occurs at higher frequencies; complex repetitive discharge on EMG may resemble myokymia, but these discharges faster and do not change in shape (seen in patients with, eg, chronic radiculopathy, chronic myopathy).

Readings

Sawlani K, Katirji B. Peripheral nerve hyperexcitability syndromes. Continuum (Minneap Minn) 2017;23 (5 Peripheral Nerve and Motor Neuron Disorders).

Disclosures

For this program, the following was disclosed: Dr. Katirji receives publishing royalties from the American Association of Neuromuscular & Electrodiagnostic Medicine, Elsevier, and Springer Nature. Unlabeled Use of Products/Investigational Use Disclosure: Dr. Katirji reports no disclosures. To view disclosures of planning committee members with relevant financial relationships, visit: audiodigest.org/continuumaudio/committee. All other members of the planning committee report nothing to disclose.

Acknowledgements

CME/CE INFO

Accreditation:

The Audio- Digest Foundation is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

The Audio- Digest Foundation designates this enduring material for a maximum of 0 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Audio Digest Foundation is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center's (ANCC's) Commission on Accreditation. Audio Digest Foundation designates this activity for 0 CE contact hours.

Lecture ID:

CA062002

Expiration:

This CME course qualifies for AMA PRA Category 1 Credits™ for 3 years from the date of publication.

Instructions:

To earn CME/CE credit for this course, you must complete all the following components in the order recommended: (1) Review introductory course content, including Educational Objectives and Faculty/Planner Disclosures; (2) Listen to the audio program and review accompanying learning materials; (3) Complete posttest (only after completing Step 2) and earn a passing score of at least 80%. Taking the course Pretest and completing the Evaluation Survey are strongly recommended (but not mandatory) components of completing this CME/CE course.

Estimated time to complete this CME/CE course:

Approximately 2x the length of the recorded lecture to account for time spent studying accompanying learning materials and completing tests.