Motor Neuron dysfunction in frontotemporal dementia

Abstract

Frontotemporal dementia and motor neuron disease share clinical, genetic and pathological characteristics. Motor neuron disease develops in a proportion of patients with frontotemporal dementia, but the incidence, severity and functional significance of motor system dysfunction in patients with frontotemporal dementia has not been determined. Neurophysiological biomarkers have been developed to document motor system dysfunction including: short-interval intracortical inhibition, a marker of corticospinal motor neuron dysfunction and the neurophysiological index, a marker of lower motor neuron dysfunction. The present study performed detailed clinical and neurophysiological assessments on 108 participants including 40 consecutive patients with frontotemporal dementia, 42 age- and gender-matched patients with motor neuron disease and 26 control subjects. Of the 40 patients with frontotemporal dementia, 12.5% had concomitant motor neuron disease. A further 27.3% of the patients with frontotemporal dementia had clinical evidence of minor motor system dysfunction such as occasional fasciculations, mild wasting or weakness. Biomarkers of motor system function were abnormal in frontotemporal dementia. Average short-interval intracortical inhibition was reduced in frontotemporal dementia (4.3 ± 1.7%) compared with controls (9.1 ± 1.1%, P < 0.05). Short-interval intracortical inhibition was particularly reduced in the progressive non-fluent aphasia subgroup, but was normal in patients with behavioural variant frontotemporal dementia and semantic dementia. The neurophysiological index was reduced in frontotemporal dementia (1.1) compared with controls (1.9, P < 0.001), indicating a degree of lower motor neuron dysfunction, although remained relatively preserved when compared with motor neuron disease (0.7, P < 0.05). Motor system dysfunction in frontotemporal dementia may result from pathological involvement of the primary motor cortex, with secondary degeneration of lower motor neurons in the brainstem and anterior horn of the spinal cord.

Is IVIg therapy warranted in progressive lower motor neuron syndromes without conduction block?

“…In addition, muscle strength of bilateral upper and lower limb muscle groups (deltoid, biceps, wrist extensors, finger flexors, finger extensors, finger abductors, hip flexors, quadriceps, tibialis anterior, and extensor hallucis longus) was assessed using the Medical Research Council scoring system and incorporated into an expanded Medical Research Council sum score (EMRCSS) developed for the detection of muscle weakness in patients with amyotrophic lateral sclerosis (ALS), with a total score of 100. 9 Laboratory investigations were performed to exclude other treatable causes of weakness including primary muscle disease, infection, vasculitis, systemic autoimmune disease, and malignancy. Anti-ganglioside M1 (GM1) antibodies and CSF were not routinely tested because they have not been shown to predict response to IVIg treatment.…”

“…IVIg treatment was continued in the remaining patients and only subsequently ceased when there was definite evidence of disease progression (8 patients, mean IVIg courses 9.9 6 1.8, range [4][5][6][7][8][9][10][11][12][13][14][15][16][17]. Irrespective of subsequent treatment, each patient was then followed in a specialized neuromuscular clinic for an average of 32.6 6 5.0 months from symptom onset (range 8-108 months), and the duration of follow-up for responders after initiation of treatment was a minimum of 12 months.…”

ECAS A-B-C: alternate forms of the Edinburgh Cognitive and Behavioural ALS Screen

“…Considerable clinical (1,2), genetic (3), pathological (4), and neuropsychological data (2-5) have demonstrated that ALS and frontotemporal dementia (FTD) significantly overlap. The observed cognitive and behavioural changes in ALS parallel those observed in frontotemporal dementia, namely, deficits in executive functions, language functions, verbal fluency, and social cognition (6)(7)(8)(9).…”

Syntactic comprehension deficits across the FTD-ALS continuum

“…Since the realisation of clinical, [1][2][3] pathological, 4,5 and genetic [6][7][8][9] overlaps between amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), studies have increasingly focussed on cognitive deficits in patients with ALS and ALS-FTD. Behavioural changes, similar to those identified in the behavioural variant of FTD, 1,10,11 and executive deficits have been well described, 12 although non-executive cognitive impairment, including language dysfunction, also occurs.…”