Hereditary Myelopathies (Spinal Cord Disorders February 2021)

Educational Objectives

The goal of this program is to improve management of spinal cord disorders. After hearing and assimilating this program, the clinician will be better able to:

1. Identify regions of the spinal cord and central nervous system commonly affected by hereditary myelopathies.

2. Develop a differential diagnosis for common hereditary myelopathies based on their clinical presentation and pattern of sensory and motor dysfunction.

Summary

Hereditary myelopathy: A group of diverse conditions involving structures within the spinal cord and possibly beyond it; abnormalities involving the spinal cord cause the major symptoms; many hereditary myelopathies affect structures outside the spinal cord (eg, cerebellum, peripheral nerves); the recognition of hereditary myelopathies guides the differential diagnosis.

Spinocerebellar degeneration: The degree of relative involvement of the spine and cerebellum varies between disorders and within the same disorder; spinal involvement includes abnormalities in upper motor neurons or the dorsal column (proprioception and sensation of vibration), or both; cerebellar abnormalities include midline abnormalities that affect the trunk, gait, speech, and eye movements; hemispheric abnormalities that affect coordination of the upper extremities; or both; many disorders also affect the peripheral nerves and other parts of the brain.

Motor neuron disorders: Associated with various degrees of impairment of the primary motor neurons in the motor cortex, degeneration of the axons of upper motor neurons emanating from the motor cortex, and abnormalities of lower motor neurons (eg, degeneration of anterior horn cells); spinal muscular atrophies — abnormalities are limited to anterior horn cells; most forms are associated with mutations in the survival motor neuron gene; primary lateral sclerosis — associated with a minor degree of degeneration of motor neurons in the motor cortex; degeneration of axons of upper motor neurons is the predominant pathology, and its severity is greatest in the corticospinal and corticobulbar tracts within the brainstem and spinal cord; unlike in many other myelopathies, sensory involvement is minimal or absent; the minimal or late involvement of lower motor neurons differentiates primary lateral sclerosis from amyotrophic lateral sclerosis.

Hereditary spastic paraplegias: Comprise nearly 100 conditions; unlike in primary lateral sclerosis, motor and sensory involvement are often present simultaneously; sensory involvement typically is characterized by mild impairment of the dorsal column; patients with motor involvement typically present with impairment of the upper motor neurons that affects long endings of the corticospinal tract in the distal thoracic cord; sensory involvement causes mild impairment in perception of vibration and proprioception that causes mild impairment of balance; the longest axons in the central nervous system are affected; distal degeneration of long motor and sensory fibers in the central nervous system is parallel to the pattern of axon degeneration in Charcot-Marie-Tooth disease type 2 (that degeneration affects distal motor and sensory axons in the peripheral nervous system); on clinical examination, the degree of impairment in proprioception and perception of vibration is minimal (patients with severe impairment in the dorsal column are more likely to have a deficiency in vitamin B12 or copper, or Friedreich ataxia).

Leukodystrophies: Characterized by abnormalities in white matter; the diversity in biochemistry and clinical symptoms is broad; in some types, patients present with chiefly encephalopathy characterized by impairments in cognition, vision, and hearing; dementia and seizures are late characteristics; in other types, encephalopathic features are late findings; spasticity in the legs is the main presenting feature and is caused by impairment in upper motor neurons (primarily in the spinal cord).

Adrenomyeloneuropathy: An adrenoleukodystrophy (a disorder characterized by an inflammatory demyelination that appears to be a reaction to underlying degeneration of axons); a minority of individuals who have adrenomyeloneuropathy develop demyelinating leukodystrophy; in the majority, adrenomyeloneuropathy is an axon degeneration disorder that resembles hereditary spastic paraplegia.

Mutations in the proteolipid protein gene: Pelizaeus-Merzbacher disease is a severe dysmyelinating, X-linked, infantile-onset disorder that causes hypotonicity; however, mutations in the same gene can cause a myelopathy that begins in adolescence or early adulthood and is characterized by a slowly progressive spastic gait; in patients who have adult-onset adrenomyeloneuropathy and a mutation in the proteolipid protein gene, degeneration of axons occurs primarily in the spinal cord and is caused by an abnormality in glial cells (the proteolipid protein gene is expressed in myelinating glial cells of the spinal cord, and that abnormality leads to degeneration of axons).

Considerations for diagnosis: Clinical signs of leukodystrophies are associated with damage to axons caused by the demyelinating abnormality; many forms of leukodystrophy are recognized not as encephalopathic disorders but instead as primarily disorders with spastic gait and myelopathy; however, MRI may reveal features of encephalopathy and demyelination of the brain late in the course of leukodystrophies.

Readings

Hereditary Myelopathy

Fink JK. Hereditary myelopathies. Continuum (Minneap Minn) 2021;27(1, Spinal Cord Disorders).

Disclosures

For this program, the following was disclosed: Dr. Fink has served as a medical advisor for the Spastic Paraplegia Foundation and as a consultant for Cure AP-4, Inc. Dr. Fink receives research/grant support from the Spastic Paraplegia Foundation and patent royalties and has provided expert medicolegal consultation.

Unlabeled Use of Products/Investigational Use Disclosure: Dr. Fink reports no disclosure.

To view disclosures of planning committee members with relevant financial relationships, visit: legacy.audio-digest.org/continuumaudio/committee. All other members of the planning committee report nothing to disclose.

The material presented in Continuum Audio has been made available by the AAN for educational purposes only and is not intended to represent the only method or procedure for the medical situations discussed but rather to present an approach, view, statement, or opinion of the speaker(s), which may be helpful to others who face similar situations. Opinions expressed by the speakers are not necessarily those of the AAN, its affiliates, or the publisher. The AAN, its affiliates, and the publisher disclaim any liability to any party for the accuracy, completeness, efficacy, or availability of the material contained in this program (including drug dosages) or for any damages arising out of the use or nonuse of any of the material contained in this program.

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:

CA100108

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.