Imaging Findings Associated with Cognitive Performance in Primary Lateral Sclerosis and Amyotrophic Lateral Sclerosis

Meoded, Avner; Kwan, Justin; Peters, Tracy L.; Huey, Edward D.; Danielian, Laura E.; Wiggs, Edythe; Morrissette, Arthur E.; Wu, Tianxia; Russell, James W.; Bayat, Elham; Grafman, Jordan; Floeter, Mary Kay

doi:10.1159/000353456

Cited by 31 publications

(27 citation statements)

References 66 publications

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“…Clinical measures of cognitive status were not associated with PBA. Although previous studies found alterations in extramotor cortical areas associated with cognitive dysfunction in ALS or PLS, 11,38 the primary structural correlates seem to be interhemispheric long association tracts. However, an association between oral naming and integrity of portions of cerebellar white matter was reported in one recent study 39 that defined cognitive impairment in PLS less stringently than consensus criteria and did not assess for concurrent PBA.…”

Section: Statistical Analysis Of Clinical Data Continuous Demographicmentioning

confidence: 66%

Impaired corticopontocerebellar tracts underlie pseudobulbar affect in motor neuron disorders

et al. 2014

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Objective: The objectives of the study were (1) to determine the prevalence and characteristics of pseudobulbar affect (PBA) in patients with primary lateral sclerosis (PLS) and amyotrophic lateral sclerosis (ALS) in an outpatient clinic population, and (2) to test the hypothesis that damage of inputs to the cerebellum, leading to cerebellar dysmodulation, is associated with PBA.Methods: Chart review of all patients with PLS and ALS seen between 2000 and 2013. The examining neurologist documented the presence or absence of PBA in 87 patients. Fortyseven patients also had diffusion tensor imaging (DTI) studies. Tract-based spatial statistics were used to compare DTI of patients with and without PBA to identify altered white matter tracts associated with PBA.Results: Thirty-one of 50 patients with PLS and 12 of 37 patients with ALS had PBA. Psychiatric/emotional assessment found congruence between mood and affect during episodes, but excessive magnitude of the response. DTI studies of 25 PLS and 22 ALS patient brains showed reduced fractional anisotropy of the corticospinal and callosal white matter tracts in all patients. Patients with PBA additionally had increased mean diffusivity of white matter tracts underlying the frontotemporal cortex, the transverse pontine fibers, and the middle cerebellar peduncle.Conclusions: PBA is common in PLS. Imaging findings showing disruption of corticopontocerebellar pathways support the hypothesis that PBA can be viewed as a "dysmetria" of emotional expression resulting from cerebellar dysmodulation. Neurology ® 2014;83:620-627 GLOSSARY ALS 5 amyotrophic lateral sclerosis; ALSbi 5 amyotrophic lateral sclerosis with mild behavioral impairment; ALSci 5 amyotrophic lateral sclerosis with mild cognitive impairment; ALSFRS-R 5 Amyotrophic Lateral Sclerosis Functional Rating Scale-revised; BDI-II 5 Beck Depression Inventory-II; DRS-2 5 Mattis Dementia Rating Scale-2; DTI 5 diffusion tensor imaging; FA 5 fractional anisotropy; FSL 5 FMRIB's Software Library; PBA 5 pseudobulbar affect; PLS 5 primary lateral sclerosis; TFCE 5 threshold-free cluster enhancement; UCLA 5 University of California Los Angeles.Pseudobulbar affect (PBA) is a syndrome of involuntary emotional expression dissociated from one's true emotional experience.1 It occurs in several neurologic disorders, including amyotrophic lateral sclerosis (ALS).2,3 In one retrospective series, PBA occurred in 50% of patients with ALS. 4 There have been case reports of PBA in patients with primary lateral sclerosis (PLS), a motor neuron disorder variant with relatively selective degeneration of upper motor neurons. However, the prevalence of PBA in PLS has not been evaluated in a large patient series. 2,6 To assess the occurrence of PBA in PLS, we reviewed the charts of all patients seen in an upper motor neuron disorder clinic.Two hypotheses have been proposed regarding the neural circuits that produce PBA. Wilson 7 proposed that brainstem centers controlling laughter and crying were separately controlled by volitional a...

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Section: Statistical Analysis Of Clinical Data Continuous Demographicmentioning

confidence: 66%

Impaired corticopontocerebellar tracts underlie pseudobulbar affect in motor neuron disorders

et al. 2014

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“…18,28 Most DTI studies have not found significant group level differences outside motor tracts in DTI, however, in patients who have mild cognitive impairment, small and scattered diffusion changes may be seen in extramotor association tracts. 30,31 MRI sequences specific for myelin also show a broader distribution of white matter changes than are seen with DTI. 32 …”

Section: Diagnosismentioning

confidence: 95%

Primary Lateral Sclerosis

et al. 2015

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Synopsis Primary lateral sclerosis (PLS) is characterized by insidious onset of progressive upper motor neuron dysfunction in the absence of clinical signs of lower motor neuron involvement. Patients experience stiffness, decreased balance and coordination, and mild weakness, and if the bulbar region is affected, difficulty speaking and swallowing, and emotional lability. The diagnosis is made based on clinical history, typical exam findings, and diagnostic testing negative for other causes of upper motor neuron dysfunction. EMG is normal, or only shows mild neurogenic findings in a few muscles, not meeting El Escorial criteria. Although no test is specific for PLS, some neurodiagnostic tests are supportive: including absent or delayed central motor conduction times; and changes in the precentral gyrus or corticospinal tracts on MRI, DTI or MR Spectroscopy. Treatment is largely supportive, and includes medications for spasticity, baclofen pump, and treatment for pseudobulbar affect. The prognosis in PLS is more benign than ALS, making this a useful diagnostic category.

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“…80 Investigations of cognitive deficits in ALS, FTD and ALS-FTD patients have been found to covary with reduction of GM in several regions of the temporal lobes, including the hippocampal formation and amygdala as well as a loss of integrity of the WM networks connecting frontotemporal areas to parietal and occipital areas, including uncinate and longitudinal fasciculus. 9,54,[81][82][83][84][85][86][87][88][89][90][91][92][93] Episodic memory Amnesia, in particular, is problematic as a symptom in ALS and FTD, as it is currently considered as the diagnosis gold standard for underlying Alzheimer's disease pathophysiology. By contrast, episodic memory is considered to be preserved in the ALS-FTD spectrum and therefore, severe amnesia is even stated as a diagnostic exclusion criterion for the behavioural variant of FTD.…”

Section: Clinical/neuropsychological Findingsmentioning

confidence: 99%

How predictive are temporal lobe changes of underlying TDP-43 pathology in the ALS-FTD continuum?

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Bertoux

Souza

et al. 2017

Ann Clin Neurophysiol

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Detection of underling proteinopathies is becoming increasingly important across neurodegenerative conditions due to upcoming disease intervention trials. In this review, we explored how temporal lobe changes in amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) can potentially predict underlying TDP-43 pathology subtypes in FTD. To date, emphasis has been given to frontal lobe changes in the study of the cognitive and behavioural impairments in both syndromes but an increasing number of pathological, imaging and neuropsychological studies suggest how temporal lobe changes could critically affect the cognition and behaviour of these conditions. In this current article, we reviewed pathological, imaging as well as clinical/neuropsychological findings of temporal involvement in the ALS-FTD continuum, how they relate to temporal lobe changes and the underlying TDP-43 pathology in FTD. Findings across studies show that TDP-43 pathology occurs and coincides in many structures in ALS and FTD, but especially in the temporal lobes. In particular, anterior and medial temporal lobes atrophy is consistently found in ALS and FTD. In addition, memory and language impairment as well as emotional and Theory of Mind processing deficits that are characteristics of the two diseases are highly correlated to temporal lobe dysfunction. We conclude by showing that temporal lobe changes due to TDP-43 type B might be particular predictive of TDP-43 type B pathology in behavioural variant FTD, which clearly needs to be investigated further in the future.

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Imaging Findings Associated with Cognitive Performance in Primary Lateral Sclerosis and Amyotrophic Lateral Sclerosis

Cited by 31 publications

References 66 publications

Impaired corticopontocerebellar tracts underlie pseudobulbar affect in motor neuron disorders

Impaired corticopontocerebellar tracts underlie pseudobulbar affect in motor neuron disorders

Primary Lateral Sclerosis

How predictive are temporal lobe changes of underlying TDP-43 pathology in the ALS-FTD continuum?

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