Peripheral nerve atrophy together with higher cerebrospinal fluid progranulin indicate axonal damage in amyotrophic lateral sclerosis

Schreiber, Stefanie; Dębska–Vielhaber, Grażyna; Abdulla, Susanne; Machts, Judith; Schreiber, Frank; Kropf, Siegfried; Körtvelyessy, Péter; Körner, Sonja; Kollewe, Katja; Petri, Susanne; Dengler, Reinhard; Kunz, Wolfram S.; Nestor, Peter J.; Vielhaber, Stefan

doi:10.1002/mus.25682

Cited by 18 publications

(13 citation statements)

References 44 publications

(127 reference statements)

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“…The mean CSF PGRN level of our MSD‐based assay (1,007 pg/ml) was similar to that published with other assays (Huchtemann et al , ; Zhou et al , ; Berghoff et al , ; Meeter et al , ; Kimura et al , ; Schreiber et al , ), albeit lower than those measured by the more widely used commercial assay from Adipogen (Ghidoni et al , ; De Riz et al , ; Vercellino et al , ; Nicholson et al , ; Morenas‐Rodríguez et al , ; Feneberg et al , ; Molgaard et al , ; Willemse et al , ; Wilke et al , ). We therefore compared our MSD‐based ELISA with that from Adipogen (cat.…”

Section: Methodssupporting

confidence: 84%

CSF progranulin increases in the course of Alzheimer's disease and is associated with sTREM 2, neurodegeneration and cognitive decline

et al. 2018

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Progranulin (PGRN) is predominantly expressed by microglia in the brain, and genetic and experimental evidence suggests a critical role in Alzheimer's disease (AD). We asked whether PGRN expression is changed in a disease severity‐specific manner in AD. We measured PGRN in cerebrospinal fluid (CSF) in two of the best‐characterized AD patient cohorts, namely the Dominant Inherited Alzheimer's Disease Network (DIAN) and the Alzheimer's Disease Neuroimaging Initiative (ADNI). In carriers of AD causing dominant mutations, cross‐sectionally assessed CSF PGRN increased over the course of the disease and significantly differed from non‐carriers 10 years before the expected symptom onset. In late‐onset AD, higher CSF PGRN was associated with more advanced disease stages and cognitive impairment. Higher CSF PGRN was associated with higher CSF soluble TREM2 (triggering receptor expressed on myeloid cells 2) only when there was underlying pathology, but not in controls. In conclusion, we demonstrate that, although CSF PGRN is not a diagnostic biomarker for AD, it may together with sTREM2 reflect microglial activation during the disease.

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Section: Methodssupporting

confidence: 84%

CSF progranulin increases in the course of Alzheimer's disease and is associated with sTREM 2, neurodegeneration and cognitive decline

et al. 2018

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“…Despite the subtle differences seen, nerve size measures still hold promise as a biomarker. Schreiber et al (2018) demonstrated correlations between peripheral nerve size and cerebrospinal fluid (CSF) progranulin levels. 46 They noted a combination of reduced nerve size and higher CSF progranulin levels were linked to lower CMAP amplitudes, suggesting the 2 markers are linked with axonal damage.…”

Section: Peripheral Nerve Ultrasound In Alsmentioning

confidence: 99%

Ultrasound in the Diagnosis and Monitoring of Amyotrophic Lateral Sclerosis: A Review

Hobson‐Webb

Simmons

2019

Muscle and Nerve

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Neuromuscular ultrasound is complementary to electrodiagnostic (EDx) testing and is useful in enhancing the diagnosis of mononeuropathies, peripheral nerve trauma, and demyelinating polyneuropathies. There is increasing interest in using ultrasound both to aid in the diagnosis of amyotrophic lateral sclerosis (ALS) and to monitor its progression. In this article we review the relevant literature on ultrasound in ALS. Ultrasound is more sensitive than EDx in identifying fasciculations in patients with ALS. It can detect decreased muscle thickness, increased muscle echointensity and echovariance, and reduced peripheral nerve size in these patients. Ultrasound is also a helpful tool in assessment of diaphragm function. Although additional studies are required to define the exact role of ultrasound in the evaluation and monitoring of ALS, it can improve the diagnostic yield in patients when ALS is suspected, but insufficiently supported, by clinical and EDx examinations. Muscle Nerve 60: 114–123, 2019

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“…The reason for the absence of CSF data in that training cohort was that lumbar puncture had been performed in another hospital (n = 48, 79%) or that no lumbar puncture had been performed (n = 7, 12%); reasons for missing CSF data could not be elucidated (n = 6, 10%). Among the 173 patients, 133 (77%) had been included in our previous peripheral nerve sonography ALS studies 13,15,26,27 Table 1 presents the demographics of the sample. There were no group differences with respect to age, sex, height, and weight.…”

Section: Samplementioning

confidence: 99%

Toward in vivo determination of peripheral nervous system immune activity in amyotrophic lateral sclerosis

Schreiber

Garz

et al. 2019

Muscle and Nerve

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Introduction: We sought to identify patients with amyotrophic lateral sclerosis (ALS) who displayed suspected peripheral nervous system (PNS) inflammation to compare them to those with suspected PNS degeneration. Methods: We measured sonographic median and ulnar nerve cross‐sectional area (CSA) and cerebrospinal fluid albumin/serum albumin ratio (Qalb) in patients with ALS to classify them as having suspected PNS degeneration (small CSA/low Qalb) or inflammation (larger CSA/high Qalb). Results: Fifty‐seven percent of patients had suspected PNS degeneration, 21% had suspected PNS inflammation, and 21% displayed suspected “normal PNS state.” Suspected PNS degeneration was related to classic ALS, shorter disease duration, and a smaller hypoechoic nerve area. Suspected PNS inflammation was associated with men, longer disease duration, and a larger hypoechoic nerve area and was the dominant finding in superoxide dismutase 1 mutation carriers. Discussion: Our simple approach might aid in the in vivo differentiation of supposed ALS subtypes, those with suspected PNS degeneration vs. inflammation, for stratification in clinical trials. Muscle Nerve 59:567–567, 2019

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Peripheral nerve atrophy together with higher cerebrospinal fluid progranulin indicate axonal damage in amyotrophic lateral sclerosis

Abstract: In ALS, the constellation of peripheral nerve atrophy together with higher CSF PGRN levels indicates pronounced axonal damage. Muscle Nerve 57: 273-278, 2018.

Cited by 18 publications

References 44 publications

CSF progranulin increases in the course of Alzheimer's disease and is associated with sTREM 2, neurodegeneration and cognitive decline

CSF progranulin increases in the course of Alzheimer's disease and is associated with sTREM 2, neurodegeneration and cognitive decline

Ultrasound in the Diagnosis and Monitoring of Amyotrophic Lateral Sclerosis: A Review

Toward in vivo determination of peripheral nervous system immune activity in amyotrophic lateral sclerosis

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