Andreas Oldag

Sonography of the median nerve in CMT1A, CMT2A, CMTX, and HNPP

Introduction: In this study we compare the ultrasound features in the median nerve in patients with different types of Charcot–Marie–Tooth (CMT) disease and hereditary neuropathies with liability to pressure palsies (HNPP) as a typical entrapment neuropathy. Methods: Median nerve ultrasound and conduction studies were performed in patients with CMT1A (n = 12), MFN2‐associated CMT2A (n = 7), CMTX (n = 5), and HNPP (n = 5), and in controls (n = 28). Results: Median nerve cross‐sectional area (CSA) was significantly increased in CMT1A, whereas, in axonal CMT2A, fascicle diameter (FD) was enlarged. CSA correlated with nerve conduction slowing in CMT1A and with axonal loss, as shown by motor and sensory nerve amplitudes in both CMT1A and CMT2A. A relatively low wrist‐to‐forearm‐ratio (WFR <0.8) or a relatively high WFR (>1.8) appeared to be unlikely in MFN2 and Cx32 mutations of CMT2A and CMTX, respectively. Conclusion: Differences in CSA, FD, and WFR of the median nerve can be helpful in defining subtypes of hereditary neuropathies. Muscle Nerve 47:385‐395, 2013

Stases are associated with blood–brain barrier damage and a restricted activation of coagulation in SHRSP

Cerebral small vessel disease (CSVD) is a chronically proceeding pathology of small brain vessels associated with white matter lesions, lacunar infarcts, brain atrophy and microbleeds. CSVD leads to slowly increasing cognitive and functional deficits but may also cause stroke-like symptoms, if vessels in critical brain areas are affected. Spontaneously hypertensive stroke-prone rats (SHRSP) exhibit several vascular risk factors, develop infarcts and hemorrhages and therefore represent a relevant model for the study of CSVD. Using this animal model, we recently demonstrated that intravasal accumulations of erythrocytes, we interpreted as stases, stand at the beginning of a pathological vascular cascade. After stases microbleeds occur, which are followed by reactive microthromboses. Bleeds and thromboses finally cause hemorrhagic infarcts. Immunohistochemical stainings show, that plasma proteins like IgG are deposited in the walls of vessels affected by stases. Further, we found small clots and thread-shaped aggregations of thrombocytes as well as thread-shaped structures of von Willebrand-Factor within stases. Thus, we conclude that blood-brain barrier damages occur in the neighborhood of stases and stases seem to be associated with a restricted activation of blood coagulation without formation of obstructive thromboses. Finally, we demonstrate that small vessel damage rarely appears in the cerebellum. Even animals with multiple cerebral infarcts may be free of any cerebellar vascular pathology.

Peripheral nerve ultrasound in amyotrophic lateral sclerosis phenotypes

Introduction: In this study we sought to determine the cross‐sectional area (CSA) of peripheral nerves in patients with distinct subtypes of amyotrophic lateral sclerosis (ALS). Methods: Ulnar and median nerve ultrasound was performed in 78 ALS patients [classic, n = 21; upper motor neuron dominant (UMND), n = 14; lower motor neuron dominant (LMND), n = 20; bulbar, n = 15; primary lateral sclerosis (PLS), n = 8] and 18 matched healthy controls. Results: Compared with controls, ALS patients had significant, distally pronounced reductions of ulnar CSA (forearm/wrist level) across all disease groups, except for PLS. Median nerve CSA (forearm/wrist level) did not differ between controls and ALS. Conclusion: Ulnar nerve ultrasound in ALS subgroups revealed significant differences in distal CSA values, which suggests it has value as a marker of LMN involvement. Its potential was particularly evident in the UMND and PLS groups, which can be hard to separate clinically, yet their accurate separation has major prognostic implications. Muscle Nerve 51:669–675, 2015

Assessment of Cortical Hemodynamics by Multichannel Near-Infrared Spectroscopy in Steno-Occlusive Disease of the Middle Cerebral Artery

Background and Purpose— In a pilot study we evaluated near-infrared spectroscopy as to its potential benefit in monitoring patients with steno-occlusive disease of a major cerebral artery for alterations in cortical hemodynamics. Methods— Cortical maps of time-to-peak (TTP) in 10 patients unilaterally affected by severe stenosis or occlusion of the middle cerebral artery were acquired by multichannel near-infrared spectroscopy after bolus application of indocyanine green. Hemodynamic manifestations were assessed by comparison between affected and unaffected hemisphere and evaluated for common constituents by principal component analysis. In one patient, TTP values were compared with those obtained by dynamic susceptibility contrast imaging. Results— TTP was increased on the affected hemisphere in 9 patients. Mean difference in TTP between hemispheres was 0.44 second (P<0.05) as compared with a mean lateral difference of 0.12 second found in a control group of 10 individuals. In group analysis a significant rise in TTP was found in the distribution of the affected middle cerebral artery, whereas principal component analysis suggests augmentation of hemodynamic effects toward the border zones as a dominant pattern. A linear correlation of 0.61 between TTP values determined by dynamic susceptibility contrast MRI and near-infrared spectroscopy was found to be statistically significant (P<0.001). Conclusion— Multichannel near-infrared spectroscopy might facilitate detection of disease-related hemodynamic changes as yet only accessible by tomographic imaging modalities. Being indicative for hypoperfusion and collateral flow increased values of TTP, as found to a varying extent in the present patient group, might be of clinical relevance.

Interhemispheric connectivity in amyotrophic lateral sclerosis: A near-infrared spectroscopy and diffusion tensor imaging study

Purpose Aim of the present study was to investigate potential impairment of non-motor areas in amyotrophic lateral sclerosis (ALS) using near-infrared spectroscopy (NIRS) and diffusion tensor imaging (DTI). In particular, we evaluated whether homotopic resting-state functional connectivity (rs-FC) of non-motor associated cortical areas correlates with clinical parameters and disease-specific degeneration of the corpus callosum (CC) in ALS. Material and methods Interhemispheric homotopic rs-FC was assessed in 31 patients and 30 healthy controls (HCs) for 8 cortical sites, from prefrontal to occipital cortex, using NIRS. DTI was performed in a subgroup of 21 patients. All patients were evaluated for cognitive dysfunction in the executive, memory, and visuospatial domains. Results ALS patients displayed an altered spatial pattern of correlation between homotopic rs-FC values when compared to HCs (p = 0.000013). In patients without executive dysfunction a strong correlation existed between the rate of motor decline and homotopic rs-FC of the anterior temporal lobes (ATLs) (ρ = − 0.85, p = 0.0004). Furthermore, antero-temporal homotopic rs-FC correlated with fractional anisotropy in the central corpus callosum (CC), corticospinal tracts (CSTs), and forceps minor as determined by DTI (p < 0.05). Conclusions The present study further supports involvement of non-motor areas in ALS. Our results render homotopic rs-FC as assessed by NIRS a potential clinical marker for disease progression rate in ALS patients without executive dysfunction and a potential anatomical marker for ALS-specific degeneration of the CC and CSTs.

Do basophile structures as age dependent phenomenon indicate small vessel wall damage

Here we demonstrate basophile structures located in the arteriolar wall and being associated with a plasma-protein-leakage. We assume, that the structures indicate blood-brain-barrier-disturbances and degenerative small vessel wall alterations.