Despite an early understanding of amyotrophic lateral sclerosis (ALS) as a disease affecting the motor system, including motoneurons in the motor cortex, brainstem, and spinal cord, today, many cases involving dementia and behavioral disorders are reported. Therefore, we currently divide ALS not only based on genetic predisposition into the most common sporadic variant (90% of cases) and the familial variant (10%), but also based on cognitive and/or behavioral symptoms, with five specific subgroups of clinical manifestation-ALS with cognitive impairment, ALS with behavioral impairment, ALS with combined cognitive and behavioral impairment, the fully developed behavioral variant of frontotemporal dementia in combination with ALS, and comorbid ALS and Alzheimer's disease (AD). Generally, these cases are referred to as amyotrophic lateral sclerosis-frontotemporal spectrum disorder (ALS-FTSD). Clinical behaviors and the presence of the same pathognomonic deposits suggest that FTLD and ALS could be a continuum of one entity. This review was designed primarily to compare neuropathological findings in different types of ALS relative to their characteristic locations as well as the immunoreactivity of the inclusions, and thus, foster a better understanding of the immunoreactivity, distribution, and morphology of the pathological deposits in relation to genetic mutations, which can be useful in specifying the final diagnosis.

• Keywords
• ALS-FTSD, amyotrophic lateral sclerosis, amyotrophic lateral sclerosis-frontotemporal spectrum disorder, familial ALS, frontotemporal lobar degeneration, motor neuron disease, sporadic ALS,
• Publication type
• Journal Article MeSH
• Review MeSH

Amyotrophic lateral sclerosis (ALS) is a devastating, uniformly lethal progressive degenerative disorder of motor neurons that overlaps with frontotemporal lobar degeneration (FTLD) clinically, morphologically, and genetically. Although many distinct mutations in various genes are known to cause amyotrophic lateral sclerosis, it remains poorly understood how they selectively impact motor neuron biology and whether they converge on common pathways to cause neuronal degeneration. Many of the gene mutations are in proteins that share similar functions. They can be grouped into those associated with cell axon dynamics and those associated with cellular phagocytic machinery, namely protein aggregation and metabolism, apoptosis, and intracellular nucleic acid transport. Analysis of pathways implicated by mutant ALS genes has provided new insights into the pathogenesis of both familial forms of ALS (fALS) and sporadic forms (sALS), although, regrettably, this has not yet yielded definitive treatments. Many genes play an important role, with TARDBP, SQSTM1, VCP, FUS, TBK1, CHCHD10, and most importantly, C9orf72 being critical genetic players in these neurological disorders. In this mini-review, we will focus on the molecular mechanisms of these two diseases.

• Keywords
• amyotrophic lateral sclerosis, frontotemporal dementia, genetics, neuropathology,
• Publication type
• Journal Article MeSH
• Review MeSH

OBJECT: To evaluate the potential of quantitative MR techniques [voxel-based morphometry (VBM), T2-relaxometry, mean diffusivity (MD), fractional anisotropy (FA)] in the diagnostics of amyotrophic lateral sclerosis (ALS). MATERIALS AND METHODS: Thirty-three ALS patients and thirty age- and sex-matched healthy volunteers were included in the cross-sectional study. T1WI, T2WI and T2 relaxometry sequences were performed at 1.5T. DWI was performed in a subgroup of 12 patients. Disease severity was estimated with the ALS Functional Rating Scale (ALS-FRS). RESULTS: We detected decreased T2 relaxation rate (R2) in the frontal white matter (FWM) (left and right P < 0.005) and caudate nucleus (left P < 0.005) in ALS patients. R2 in the FWM correlated with age in patients and controls. A correlation (P < 0.01, cluster-level corrected) between atrophy in the corona radiata and the limb ALS-FRS subset was found, as well as a difference between patients and controls in this area. No correlation between FA/MD and ALS-FRS was observed in the T2 hyperintense region of the posterior limb of the internal capsule (PLIC), or in the site of atrophy detected by VBM. No R2 or PD changes in the PLIC were detected. TBSS revealed decreased FA in the corona radiata and callosal body. CONCLUSIONS: Decreased R2 in the left caudate and bilateral FWM may help in the diagnostic process and disqualifies these regions as internal controls in ALS studies. The PLIC is not a reliable diagnostic marker of ALS.

• MeSH
• Amyotrophic Lateral Sclerosis diagnosis   MeSH
• Diffusion Magnetic Resonance Imaging methods   MeSH
• Middle Aged MeSH
• Humans MeSH
• Brain pathology   MeSH
• Cross-Sectional Studies MeSH
• Aged MeSH
• Severity of Illness Index MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Evaluation Study MeSH
• Research Support, Non-U.S. Gov't MeSH

BACKGROUND: Definite Alzheimer's disease (AD) requires neuropathological confirmation. Single-photon emission computed tomography (SPECT) may enhance diagnostic accuracy, but due to restricted sensitivity and specificity, the role of SPECT is largely limited with regard to this purpose. METHODS: We propose a new method of SPECT data analysis. The method is based on a combination of parietal lobe selection (as regions-of-interest (ROI)), 3D fuzzy edge detection, and 3D watershed transformation. We applied the algorithm to three-dimensional SPECT images of human brains and compared the number of watershed regions inside the ROI between AD patients and controls. The Student's two-sample t-test was used for testing domain number equity in both groups. RESULTS: AD patients had a significantly reduced number of watershed regions compared to controls (p < 0.01). A sensitivity of 94.1% and specificity of 80% was obtained with a threshold value of 57.11 for the watershed domain number. The narrowing of the SPECT analysis to parietal regions leads to a substantial increase in both sensitivity and specificity. CONCLUSIONS: Our non-invasive, relatively low-cost, and easy method can contribute to a more precise diagnosis of AD.

• MeSH
• Algorithms * MeSH
• Alzheimer Disease diagnostic imaging   MeSH
• Fuzzy Logic * MeSH
• Image Interpretation, Computer-Assisted methods   MeSH
• Tomography, Emission-Computed, Single-Photon methods   MeSH
• Middle Aged MeSH
• Humans MeSH
• Brain diagnostic imaging   MeSH
• Reproducibility of Results MeSH
• Retrospective Studies MeSH
• Pattern Recognition, Automated methods   MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Sensitivity and Specificity MeSH
• Image Enhancement methods   MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH