FTD with Motor Neuron Disease (FTD/MND)

Researchers have begun to recognize an important connection between frontotemporal degeneration (FTD) and amyotrophic lateral sclerosis (ALS, or Lou Gehrig’s disease). FTD is a syndrome of progressive changes in behavior and language due to loss of function of neurons in the frontal and temporal lobes. Usually, FTD has relatively little effect on the parts of the nervous system that control movement, and so many FTD patients remain physically strong and relatively agile until late in the illness. However, in about 10-15% of patients with FTD, the disease also involves the nerve cells controlling voluntary movement, called motor neurons. When this occurs, the syndrome is called FTD with motor neuron disease (FTD/MND) or FTD with ALS.

Patients with FTD/MND may present with the same behavioral and/or language changes seen in other subtypes of FTD. In this syndrome however, these changes are accompanied by a deterioration of motor neurons that manifest as weakness in the muscles with stiffness, difficulty making fine movements, atrophy (shrinkage) of the muscles, and fine muscle twitches and cramps. Muscle changes can affect the arms and/or legs on one or both sides of the body, or the face, tongue and mouth, depending on how the nervous system is affected in that individual. As the disease worsens, more parts of the motor system become involved.

Approximately 30% of ALS patients will show signs of frontal lobe decline, which affects organizational function and behavioral comportment.

Patients with FTD/MND may first present with features of either FTD or ALS with the additional symptoms developing as the disease progresses. All patients with FTD/MND will experience a gradual, steady decline in functioning.

Key Clinical Features

People with FTD/MND experience behavior and language symptoms associated with other syndromes within the frontotemporal dementias and described in other AFTD materials (FTD Overview, bvFTD, PPA, SD). The symptoms of motor neuron disease can go unnoticed for quite a while in FTD, because the changes in behavior, personality and thinking are so dramatic.

The motor symptoms arising from motor neuron disease in FTD/MND are the same as those seen in ALS. Not all of these symptoms will be seen in every patient. Rather the symptoms depend on which parts of the nervous system are involved. Motor difficulties may include:

  • Muscle weakness, which can involve the arms, legs, face, tongue or neck
  • Clumsiness with fine movements of the hands
  • Tripping or falling (due to weak or stiff legs)
  • Shortness of breath (due to weak breathing muscles)
  • Muscle atrophy (shrinkage)
  • Fasciculations (muscle twitches)
  • Muscle cramps
  • Dysphagia (difficulty swallowing, possibly with coughing because of food or saliva in the windpipe)
  • Dysarthria (slurred speech, nasal or breathy speech)
  • Spasticity (tight and stiff muscles)
  • Hyperreflexia (exaggerated reflexes), usually be noted during a physical examination.
  • Outbursts of laughing or crying that may not be appropriate to the situation or which may appear when the patient is mounting an effort to speak.

Neuroimaging studies in patients who have clear symptoms of FTD, along with MND, show atrophy of the frontal and/or temporal lobes. Nuclear medicine studies such as FDG-PET, which measures glucose use by brain, or SPECT, which usually measures cerebral blood flow, show deceases in glucose use and blood flow in the frontal and/or temporal lobes.

Key Pathologic Features

At autopsy, the frontal and temporal lobes of the brain show atrophy similar to other FTD subtypes. When viewed under the microscope, the frontal and temporal lobes, including the motor regions of the cerebral cortex, show loss of neurons and gliosis (scar tissue in the brain), and many of the remaining neurons are shrunken or abnormally shaped and are filled with globs of abnormal protein. In the past, these globs (called inclusions) were found to contain a protein called ubiquitin. Recently, it was discovered that they also contain a protein called TDP-43. There is also degeneration of motor neurons in the brain stem and spinal cord (if it is examined).

The scientific literature discussing FTD/MND can be a bit confusing, because there can be signs of problems in the motor neurons at autopsy that did not have much noticeable impact on the person while they lived. When pathologists examining the brain see these types of changes along with similar changes in the rest of the frontal and temporal lobes, they call this FTD/MND, regardless of whether the patient actually experienced any motor symptoms.

The cause of FTD/MND is unknown. However, the linkage of FTD/MND and ALS to the protein TDP-43 may be an important clue. TDP-43 seems to play a role in how the cell’s molecular code (DNA) is read and used to make proteins, which do all the work in the cells.

Genetics

Our understanding of the relationship between genes, FTD, ALS and FTD/MND is still evolving. The majority of cases of FTD/MND are not hereditary.

There is no clear genetic abnormality that is closely associated with the development of FTD/MND. Recently, a mutation in the gene encoding the protein progranulin was found to be a common cause of FTD in families with a strong family history. When patients have a progranulin mutation, they always have TDP-43 inclusions at autopsy, however surprisingly; they do not seem to develop MND. Similarly, families with mutations in the gene coding for TDP-43 gene have been found to develop ALS, but so far such patients have not been found to show signs of FTD. However, given that there are families who have several members with FTD/MND; researchers continue to search for genes that may explain the development of this combination of symptoms.

Treatment

There is no cure for FTD/MND. Riluzole, the first drug approved for use in the treatment of ALS, has been shown to slow the progression of ALS, but formal study of the effects of riluzole in FTD/MND has not been done. Other medications may help relieve the symptoms of muscle cramping and spasticity.

Management and Prognosis

Patients with this diagnosis usually experience a rapid decline in both physical and cognitive abilities. The course of FTD/MND may be as quick as 2-3 years, as opposed to the 5-10 year course more commonly seen among other FTD patients.

Physical therapy, including stretching exercises and low-impact exercise can help relieve muscle symptoms. Devices such as ramps, braces, walkers, and wheelchairs can help patients conserve energy and remain mobile. Speech therapy can help a patient develop strategies to speak more clearly. Over time alternate means of communication, such as speech synthesizers, may be of use.

The ALS features of the disorder eventually render patients unable to stand, walk, get in or out of bed on their own, or use their hands and arms. Difficulty swallowing and chewing impair the patient’s ability to eat normally and increase the risk of choking. Patients eventually lose the ability to breathe on their own and will require support on a ventilator for survival.

It is important for caregivers and families to think about long-term management issues and identify a team of experts who can help with difficult medical, financial and emotional challenges. It is imperative to have a physician who is knowledgeable about FTD and approaches to treatment. Other medical specialists who may be helpful include: speech therapists, occupational and physical therapists, neuropsychologists, nurses (especially home-care nursing) and genetic counselors.


For additional information and support:

The Association for Frontotemporal Degeneration
Radnor Station #2, Suite 320
290 King of Prussia Rd.
Radnor, PA 19087
Toll free: 866-507-7222
E-mail: info@the[email protected]
www.theaftd.org

ALS Association (ALSA)
27001 Agoura Road, Suite 150
Calabasas Hills, CA 91301-5104
(800) 782-4747
www.alsa.org