Photodynamic therapy light': An enhanced treatment protocol for actinic keratoses with minimal pain and optimal clinical outcome by combining laser-assisted low irradiance PDT with shortened daylight PDT.

Background: Between 2003 and 2016, 546 patients in our clinic discontinued outpatient treatment for actinic keratoses (AKs) using conventional photodynamic therapy (PDT) because of intolerable pain, thereby necessitating the use of a less painful procedure. Therefore, we developed a novel off-label PDT protocol: 'PDT light'.

Methods: Laser-assisted low irradiance PDT (li-PDT) was performed beginning in 2014.

Clinical spreading of muscle weakness in amyotrophic lateral sclerosis (ALS): a study in 910 patients.

Background: Neuroanatomical staging of sporadic amyotrophic lateral sclerosis (ALS) indicates that neurodegeneration may spread corticofugally.

Methods: We conducted an observational study to define the initial sites of disease onset and the clinical progression ('spreading patterns') of motor deficits in a cohort of 910 ALS patients in Germany.

Results: Mean age of ALS onset was 59.

Neuropeptide FF (NPFF)-positive nerve cells of the human cerebral cortex and white matter in controls, selected neurodegenerative diseases, and schizophrenia.

We quantified and determined for the first time the distribution pattern of the neuropeptide NPFF in the human cerebral cortex and subjacent white matter. To do so, we studied n = 9 cases without neurological disorders and n = 22 cases with neurodegenerative diseases, including sporadic amyotrophic lateral sclerosis (ALS, n = 8), Alzheimer's disease (AD, n = 8), Pick's disease (PiD, n = 3), and schizophrenia (n = 3). NPFF-immunopositive cells were located chiefly, but not exclusively, in the superficial white matter and constituted there a subpopulation of white matter interstitial cells (WMIC): Pyramidal-like and multipolar somata predominated in the gyral crowns, whereas bipolar and ovoid somata predominated in the cortex surrounding the sulci.

CLARITY increases sensitivity and specificity of fluorescence immunostaining in long-term archived human brain tissue.

Background: Post mortem human brain tissue is an essential resource to study cell types, connectivity as well as subcellular structures down to the molecular setup of the central nervous system especially with respect to the plethora of brain diseases. A key method is immunostaining with fluorescent dyes, which allows high-resolution imaging in three dimensions of multiple structures simultaneously. Although there are large collections of formalin-fixed brains, research is often limited because several conditions arise that complicate the use of human brain tissue for high-resolution fluorescence microscopy.

Differential Glial Chitotriosidase 1 and Chitinase 3-like Protein 1 Expression in the Human Primary Visual Cortex and Cerebellum after Global Hypoxia-Ischemia.

Here, we studied the neuroinflammation- and ischemia-related glial markers chitotriosidase 1 (CHIT1) and chitinase-3-like protein 1 (CHI3L1, alias YKL-40) in the human striate cortex and cerebellum at different time points after global hypoxic-ischemic brain injury (HIBI). Both regions differ considerably in their glial cell population but are supplied by the posterior circulation. CHIT1 and CHI3L1 expression was compared to changes in microglial (IBA1, CD68), astrocytic (GFAP, S100β), and neuronal markers (H&E, neurofilament heavy chain, NfH; calretinin, CALR) using immunohistochemistry and multiple-label immunofluorescence.

Neuropathology and neuroanatomy of TDP-43 amyotrophic lateral sclerosis.

Purpose Of Review: Intracellular inclusions consisting of the abnormal TDP-43 protein and its nucleocytoplasmic mislocalization in selected cell types are hallmark pathological features of sALS. Descriptive (histological, morphological), anatomical, and molecular studies all have improved our understanding of the neuropathology of sporadic amyotrophic lateral sclerosis (sALS). This review highlights some of the latest developments in the field.

Multimodal in vivo staging in amyotrophic lateral sclerosis using artificial intelligence.

Background: The underlying neuropathological process of amyotrophic lateral sclerosis (ALS) can be classified in a four-stage sequential pTDP-43 cerebral propagation scheme. Using diffusion tensor imaging (DTI), in vivo imaging of these stages has already been shown to be feasible for the specific corticoefferent tract systems. Because both cognitive and oculomotor dysfunctions are associated with microstructural changes at the brain level in ALS, a cognitive and an oculomotor staging classification were developed, respectively.

Clinicoanatomical substrates of selfish behaviour in amyotrophic lateral sclerosis - An observational cohort study.

Objective: ALS primarily affects motor functions, but cognitive functions, including social understanding, may also be impaired. Von Economo neurons (VENs) are part of the neuronal substrate of social understanding and these cells are histopathologically altered in ALS. We investigated whether activity in areas including VENs is associated with an impairment of cognitive tasks that mirror social functioning.

Involvement of cortico-efferent tracts in flail arm syndrome: a tract-of-interest-based DTI study.

Background: Flail arm syndrome is a restricted phenotype of motor neuron disease that is characterized by progressive, predominantly proximal weakness and atrophy of the upper limbs.

Objective: The study was designed to investigate specific white matter alterations in diffusion tensor imaging (DTI) data from flail arm syndrome patients using a hypothesis-guided tract-of-interest-based approach to identify in vivo microstructural changes according to a neuropathologically defined amyotrophic lateral sclerosis (ALS)-related pathology of the cortico-efferent tracts.

Methods: DTI-based white matter mapping was performed both by an unbiased voxel-wise statistical comparison and by a hypothesis-guided tract-wise analysis of fractional anisotropy (FA) maps according to the neuropathological ALS-propagation pattern for 43 flail arm syndrome patients vs 43 'classical' ALS patients vs 40 matched controls.

Anatomic survey of seeding in Alzheimer's disease brains reveals unexpected patterns.

Tauopathies are heterogeneous neurodegenerative diseases defined by progressive brain accumulation of tau aggregates. The most common tauopathy, sporadic Alzheimer's disease (AD), involves progressive tau deposition that can be divided into specific stages of neurofibrillary tangle pathology. This classification is consistent with experimental data which suggests that network-based propagation is mediated by cell-cell transfer of tau "seeds", or assemblies, that serve as templates for their own replication.

A comparative study of pre-alpha islands in the entorhinal cortex from selected primates and in lissencephaly.

The entorhinal cortex (EC) is the main interface between the sensory association areas of the neocortex and the hippocampus. It is crucial for the evaluation and processing of sensory data for long-term memory consolidation and shows damage in many brain diseases, for example, neurodegenerative diseases, such as Alzheimer's disease and developmental disorders. The pre-alpha layer of the EC in humans (layer II) displays a remarkable distribution of neurons in islands.

Seeding Propensity and Characteristics of Pathogenic αSyn Assemblies in Formalin-Fixed Human Tissue from the Enteric Nervous System, Olfactory Bulb, and Brainstem in Cases Staged for Parkinson's Disease.

We investigated α-synuclein's (αSyn) seeding activity in tissue from the brain and enteric nervous system. Specifically, we assessed the seeding propensity of pathogenic αSyn in formalin-fixed tissue from the gastric cardia and five brain regions of 29 individuals (12 Parkinson's disease, 8 incidental Lewy body disease, 9 controls) using a protein misfolding cyclic amplification assay. The structural characteristics of the resultant αSyn assemblies were determined by limited proteolysis and transmission electron microscopy.

Hypothesis: Tau pathology is an initiating factor in sporadic Alzheimer's disease.

The etiology of the common, sporadic form of Alzheimer's disease (sAD) is unknown. We hypothesize that tau pathology within select projection neurons with susceptible microenvironments can initiate sAD. This postulate rests on extensive data demonstrating that in human brains tau pathology appears about a decade before the formation of Aβ plaques (Aβps), especially targeting glutamate projection neurons in the association cortex.

Pattern of paresis in ALS is consistent with the physiology of the corticomotoneuronal projections to different muscle groups.

Objective: A recent neuroanatomical staging scheme of amyotrophic lateral sclerosis (ALS) indicates that a cortical lesion may spread, as a network disorder, both at the cortical level and via corticofugal tracts, including corticospinal projections providing direct monosynaptic input to α-motoneurons. These projections are involved preferentially and early in ALS. If these findings are clinically relevant, the pattern of paresis in ALS should primarily involve those muscle groups that receive the strongest direct corticomotoneuronal (CM) innervation.

In vivo histopathological staging in C9orf72-associated ALS: A tract of interest DTI study.

Background: Diffusion tensor imaging (DTI) can identify amyotrophic lateral sclerosis (ALS)-associated patterns of brain alterations at the group level according to a neuropathological staging system.

Objective: The study was designed to investigate the in vivo staging in ALS patients with the C9orf72 expansion and potential differences to ALS patients with the SOD1 mutation.

Methods: DTI-based white matter mapping was performed both by an unbiased voxel-wise statistical comparison and by a hypothesis-guided tract-wise analysis of fractional anisotropy (FA) maps according to the ALS-staging pattern for 27 ALS patients with C9orf72 expansion vs 15 ALS patients with SOD1 mutation vs 32 matched healthy controls.

Histological correlates of postmortem ultra-high-resolution single-section MRI in cortical cerebral microinfarcts.

The identification of cerebral microinfarctions with magnetic resonance imaging (MRI) and histological methods remains challenging in aging and dementia. Here, we matched pathological changes in the microvasculature of cortical cerebral microinfarcts to MRI signals using single 100 μm-thick histological sections scanned with ultra-high-resolution 11.7 T MRI.

Top-Down Projections Direct the Gradual Progression of Alzheimer-Related Tau Pathology Throughout the Neocortex.

In sporadic Alzheimer's disease (sAD), tau pathology gradually but relentlessly progresses from the transentorhinal region of the temporal lobe into both the allocortex and temporal high order association areas of the neocortex. From there, it ultimately reaches the primary sensory and motor fields of the neocortex. The brunt of the changes seen during neurofibrillary stages (NFT) I-VI is borne by top-down projection neurons that contribute to cortico-cortical connectivities between different neocortical fields.

Fabry Disease With Concomitant Lewy Body Disease.

Although Gaucher disease can be accompanied by Lewy pathology (LP) and extrapyramidal symptoms, it is unknown if LP exists in Fabry disease (FD), another progressive multisystem lysosomal storage disorder. We aimed to elucidate the distribution patterns of FD-related inclusions and LP in the brain of a 58-year-old cognitively unimpaired male FD patient suffering from predominant hypokinesia. Immunohistochemistry (CD77, α-synuclein, collagen IV) and neuropathological staging were performed on 100-µm sections.

From the Entorhinal Region via the Prosubiculum to the Dentate Fascia: Alzheimer Disease-Related Neurofibrillary Changes in the Temporal Allocortex.

The pathological process underlying Alzheimer disease (AD) unfolds predominantly in the cerebral cortex with the gradual appearance and regional progression of abnormal tau. Intraneuronal tau pathology progresses from the temporal transentorhinal and entorhinal regions into neocortical fields/areas of the temporal allocortex. Here, based on 95 cases staged for AD-related neurofibrillary changes, we propose an ordered progression of abnormal tau in the temporal allocortex.

To stage, or not to stage.

Staging of neurodegenerative diseases is based chiefly on the topographical or anatomical extent of aggregated proteinaceous inclusions, and the density or severity of the lesions in a given region is usually assessed semiquantitatively. Associated phenomena, such as cell loss and synapse loss, are evaluated but not staged. This article reviews the development of neuropathological staging of the sporadic Alzheimer's and sporadic Parkinson's diseases.

Longitudinal brain atrophy distribution in advanced Parkinson's disease: What makes the difference in "cognitive status" converters?

We investigated the brain atrophy distribution pattern and rate of regional atrophy change in Parkinson's disease (PD) in association with the cognitive status to identify the morphological characteristics of conversion to mild cognitive impairment (MCI) and dementia (PDD). T1-weighted longitudinal 3T MRI data (up to four follow-up assessments) from neuropsychologically well-characterized advanced PD patients (n = 172, 8.9 years disease duration) and healthy elderly controls (n = 85) enrolled in the LANDSCAPE study were longitudinally analyzed using a linear mixed effect model and atlas-based volumetry and cortical thickness measures.