Devic’s Disease – A Primer

Definition

Devic’s disease is an inflammatory disease of the central nervous system, which mainly affects the myelin sheath covering the optic nerve and spinal cord. Devic’s disease resembles multiple sclerosis, but is a distinct clinical entity.

Devic’s disease is characterized by attacks of bilateral acute optic neuritis. This maybe followed by severe transverse myelopathy (acute inflammation of the spinal cord), either at the same time along with the attacks of optic neuritis or after a period of days to months. The course of Devic’s disease maybe monophasic or relapsing.

  • Monophasic: the patients experience either unilateral or bilateral optic neuritis or a single episode of myelitis.
  • Relapsing: in this course the patients continue to have a discrete exacerbation of optic neuritis and/or myelitis.

Epidemiology

Neuromyelitis optica usually affects young adults, but also has been reported in infants. The ratio of men to women may differ according to the course of the disease. Most reports suggest a ratio of approximately 1.4 to 1.8. Neuromyelitis optica (NMO) is more common in African Americans, Japanese and other pacific islanders.

Causes

Etiology is unknown but NMO is believed to be an autoimmune disease associated with autoantibodies to aquaporin-4.

Clinical features

Devic’s syndrome consists of one or more episodes of optic neuritis in combination with myelitis.

  1. A viral prodrome precedes the onset of the disease in 30-50% of the cases. The prodrome consists of headache, fever, fatigue, myalgias and respiratory or gastrointestinal complaints.
  2. Rapid, bilateral and occasionally, complete visual loss occurs.
  3. Acute transverse myelitis, defined as, severe bilateral inflammatory spinal cord injury with neurological dysfunction worsening over several hours to days and involving sensory, motor and sphincter function is typical presentation of NMO. The acute tranverse myelitis may present with the following symptoms:
    • back and girdle pain
    • paresthesia and weakness in lower limbs
    • weakness rapidly evolves to paraplegia and or quadriplegia often causing complete sensory loss caudal to the lesion and a flaccid bladder.
    • The acute lesion usually traverses at least three contiguous vertebral segments of the spinal cord and may result in a spinal shock with flaccid weakness, absent deep tendon reflexes and mute plantar responses.
    • Other symptoms include vertigo, facial numbness, nystagmus, headache and postural tremor.

Diagnosis

  • MRI of the brain and spinal cord: during acute optic neuritis the MRI may demonstrate a swelling of the affected optic nerve or the chiasm. During acute myelitis the affected region is expanded and swollen. Heterogeneous T2 signal within the lesion may suggest cavitations and necrosis. Typically, the lesions are in the central part of the cord.
  • Cerebrospinal fluid (CSF) analysis: occasionally patients may have a pleocytosis around the time of acute myelitis exacerbation. The CSF leukocyte differential may reveal the presence of lymphocytes or neutrophils.
  • Serologic Testing: anti-NMO IgG and aquaporin-4 antibodies allow diagnosis of NMO
  • Neurophysiologic tests: visual evoked potentials may occasionally detect sub clinical optic nerve lesions.

Treatment/Prognosis

The mainstay of therapy is the treatment of acute attacks, prevention of medical complications and rehabilitation.

  • Intravenous corticosteroids are given during exacerbations of NMO.
  • Plasmapheresis is used as the second-line treatment.
  • Long-term maintenance treatments are immunosuppressive drugs (azathioprine or mycophenolate mofetil), combined with corticosteroids in some patients, or rituximab therapy.
  • Prevention of complications is important. Acute cervical cord attack may cause respiratory failure. Patients at risk of this complication may require intensive care unit observation and evaluation of respiratory and bulbar status.
  • Medical measures to prevent thromboembolic complications, aspiration pneumonia, decubiti and urinary tract infections are also required.

The prognosis is variable: patients may recover completely from individual attacks, but residual neurological deficits are common and sometimes severe.

  • Unrecognized or untreated, up to 30% of patients may die in the first 5 years of their illness of an attack of severe myelitis leading to respiratory failure.
  • A high proportion of patients will become legally blind in one or both eyes and/or have substantial residual paraparesis.

Answer to CC #12

Case challenge # 12 presented a 27 year old black female with descending numbness, paresthesias, and blurry vision. The exam confirms her complaints, and lumbar puncture reveals a lymphocytic pleocytosis. The MRI findings, seen below, reveals inflammation of the right optic nerve, but no brain parenchymal findings.

NMO MRI

What is the most likely diagnosis?

 
The correct answer is Devic’s Disease (Neuromyelitis Optica)!
  • Optic neuritis and cervical myelopathy
  • Can be difficult to distinguish from MS, but is a distinct entity
  • CSF may have neutrophilic pleocytosis, but negative for oligoclonal bands in up to 85% of cases
  • NMO-IgG binds to Aquaporin-4 channel in the astrocyte foot process at the blood-brain barrier. Testing for this antibody is both sensitive and specific.
  • No controlled trials evaluating therapy – usually IV steroids and PLEX, followed by systemic immuno-suppresion to prevent recurrent episodes.

Case challenge #13 (aka the Parkland Files!) will be posted next week!

 

 

Grand Rounds Review: Delirium

This morning, Dr. Sharon Inouye gave us an excellent overview of delirium, with a focus on acute delirium in the elderly. She is the director of the Aging Brain Institute and Professor of Medicine at the Harvard School of Medicine and Beth Isreal Deaconess Medical Center. As a leading expert in the field, Dr. Inouye developed the Confusion Assessment Method (CAM), an internationally recognized method for identifying delirium. Here is a synopsis of her talk, with salient points that directly apply to our clinical practice.

Risk Factors for Delirium

  • Underlying dementia
  • Older age
  • Co-morbid illness
  • Severity of medical illness
  • Infection
  • ‘High-risk’ medication use (see below!)
  • Diminished activities of daily living
  • Immobility
  • Sensory impairment (vision, hearing)
  • Urinary catheterization
  • Urea and electrolyte imbalance
  • Malnutrition

Potentially Inappropriate Medications for the Elderly

In 2012, the American College of Geriatrics released the Beers criteria for medications with potential harm (including risk for delirium) in the elderly – mant of the medications we most commonly use populate this list!

  • Anticholinergics
    • 1st generation antihistamines (diphenhydramine, chlorpheniramine, etc.)
    • Anti-parkinson agents (benztropine)
    • Anti-spasmodics (dicyclomine, hyoscyamine, etc.)
  • Anti-microbials (Nitrofurantoin – pulm toxicity)
  • CNS medications
    • Tricyclics (amitriptyline, imipramine, doxepin – very antichol)
    • Conventional and Atypical Anti-psychotics
    • Benzos (increased risk of cognitive impairment)
  • Sedative/Hypnotics (zolpidem, eszopiclone, etc.)
  • Anti-arrhythmics (disopyramide, etc.)
  • Antitussives (dextromethorphan, etc.)
  • Anti-vertigo meds (meclizine, etc.)
  • H2-blockers (famotidine, etc.)
  • Mydriatics (atropine, etc.)

The list goes on, for more information, click here.

Diagnosis/Identification of Delirium

The Confusion Assesment Method

CAM

(to use the CAM, click the image above to visit the HELP website)

Management

  • Non-pharmacologic measures are best! Guidelines do not recommend pharmacologic management as a first line, except for a few specific situations.
    • Re-orientation
    • Reduce medications
    • Reduce length of stay
    • Maintain day-night cycle
    • Familar surroundings and people
    • Remove catheters!
    • Maintain nutritional balance
  • Drug treatment may reduce agitation, but may prolong delirium duration and cognitive decline.
    • Pearl – reserve for patients with severe agitation which will:
      1. Cause interruption of essential medical therapy (i.e. intubation)
      2. Pose potential harm to the patient or staff
    • Recommended Approach: 
      • Haloperidol 0.25-0.50 mg PO or IM (avoid IV – short acting and can precipitate torsades de pointes)
      • Repeat dose q30 minutes until patient is manageable (maximum dose 3-5mg/24 hours)
      • Maintenance: 50% of loading dose divided over the next 24 hours
      • Taper dose of the next several days

IOM Releases Report on Cognitive Aging!

This week at morning report, we were joined by Dr. Sharon Inouye, Professor of Medicine from Harvard Medical School who specializes in geriatric medicine. She brought to our attention this week’s report on cognitive aging by the Institute of Medicine released this week, “Cognitive Aging: Progress in Understanding and Opportunities for Action”. Key points from the report below:

  • The brain is responsible for “cognition,” a term that describes mental functions including memory, decision making, processing speed, and learning. As the brain ages, these functions may change— a process called “cognitive aging.”

  • It is not the same as Alzheimer’s disease or other types of dementia. Cognitive aging is a natural, lifelong process that occurs in every individual.

  • Not everyone is the same as individuals have different effects from cognitive aging.
  • Cognitive aging should not be synonymous with deterioration – other areas may improve with aging such as wisdom, knowledge, and overall happiness.
  • The reports finds 3 areas that can maintain and improve cognition with aging
    • Physical Exercise
    • Reduced Cardiovascular Risk Factors
    • Appropriately Managing Medications and Co-Morbid Conditions That Can Affect Cognition
  • Click on the picture below to read the report as well as links for helpful resources for providers and patients!