CLINICAL of Dementia in Motor Neuron Disease

History

• FTD/MND usually presents as a change in personality with deterioration in social conduct.
  
  
  
  • Initial behavioral changes vary but include abulia, apathy, and reduced spontaneity and/or initiation.
  
  
  • Some patients become strikingly disinhibited, overactive, and frankly inappropriate with emotional lability.
  
  
  
  


• With disease progression, even those patients manifesting disinhibition and restlessness become increasingly apathetic.


• Stereotypic behavior and repetitive rituals of hoarding, dressing, wandering, and toileting can be observed.


• Patients may overeat, exhibit hyperoral tendencies, and develop food fads (although this is more exceptional); some patients may hold food in their mouth for prolonged periods without swallowing.


• Dynamic spontaneous speech output progressively declines, resulting in anarthria and mutism. Visuospatial skills are relatively spared throughout illness, but there is significant memory impairment.
  
  
  
  • A subset of patients presents with rapidly progressive aphasia.
  
  
  • Despite progression to anarthria, autopsy studies show that anarthria can occur in the absence of significant hypoglossal nucleus involvement.
  
  
  • Memory also is impaired, but this is not as distinguishing as the frontal lobe or language features.
  
  
  • Posterior cortical functions (eg, visuospatial skills) are preserved and/or spared until the preterminal stages.
  
  
  • The clinical pattern reflects the topographic pattern of atrophy, often visible radiographically, with asymmetric frontotemporal atrophy.
  
  
  • If asymmetrically worse in the left (language-dominant) hemisphere, aphasia is a likely and prominent clinical feature.
  
  
  
  


• Throughout the course of the disease, signs and symptoms of MND also progress.
  
  
  
  • Cognitive changes often precede signs of MND.
  
  
  • Limb weakness and dysphagia eventually become disabling, although some patients have a primarily bulbar pattern of weakness with relative sparing of limb strength.
  
  
  
  


• Recently, consensus clinical criteria detailing core and supportive features for FTD syndromes were published.

Physical

• Patients usually perform poorly on tests of frontal lobe function (ie, Wisconsin card sorting, picture sequencing, verbal fluency tests). Memory is impaired, but less consistently in the mild stages.


• Clinical signs of MND usually follow or accompany dementia onset. MND signs include bulbar weakness with dysarthria and dysphagia, limb weakness, muscle wasting and fasciculations, and, of greatest concern, dyspnea.


• Akinesia and rigidity are uncommon in this disorder but more common in patients with a longer interval between onset of dementia and neurologic signs (more than 24 mo in a Japanese series). This may reflect, in part, the variable involvement of the substantia nigra and other pigmented brainstem nuclei that are observed in roughly 50% of patients at autopsy. This, in turn, may vary between populations (more common in Chamorro Indians).

Causes

• Worldwide, FTD/MND is sporadic with unknown etiology.


• A minority of patients has a family history, but this overlap syndrome may be related to other neurodegenerative overlap syndromes that include variable degrees of dementia, MND, and parkinsonism.


• Familial cases of this type are linked to a mutated region of chromosome 17, which contains the tau gene. It is possible that a similar genetic association will be found for FTD/MND.