Erik Bahn

Reconstruction of single cortical projection neurons reveals primary spine loss in multiple sclerosis

Grey matter pathology has emerged as an important contributor to long-term disability in multiple sclerosis. To better understand where and how neuronal damage in the grey matter is initiated, we used high resolution confocal microscopy of Golgi-Cox impregnated tissue sections and reconstructed single cortical projection neurons in autopsies from eight patients with long-standing relapsing-remitting or secondary progressive multiple sclerosis and eight control patients without neurological disease. Analysis of several hundred individual neurons located in the insular, frontotemporal and occipital lobe revealed a widespread and pronounced loss of dendritic spines in multiple sclerosis cortex that occurs independent of cortical demyelination and axon loss. The presence of a primary synaptic pathology in the normal-appearing cortex of multiple sclerosis patients challenges current disease concepts and has important implications for our understanding of disease progression.

Decrease of S100 beta protein in serum of patients with amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease of unknown origin characterized by loss of upper and lower motor neurons and concomitant astrogliosis. We have investigated the S100 beta protein levels in serum as a marker for astroglia of patients with ALS (n = 41) in comparison to a control group (n = 32). Additionally we have investigated 12 patients at different follow-up time points (minimum 6 months). We could not observe a significant difference of S100 beta protein in patients with ALS in comparison to our control group (P = 0.11) but we could clearly see a decrease of S100 beta levels in the further course of the disease. As S100 beta is also seen as a protein with nerve growth factor activity we assume that the fall of serum levels may reflect the loss of nerve growth stimulation in patients with ALS and suppose that repetitive measurements of S100 beta in serum can be used as an objective marker for disease progression.

Elevated Serum Levels of Astroglial S100β in Patients with Liver Cirrhosis Indicate Early and Subclinical Portal-Systemic Encephalopathy

Portal-systemic encephalopathy is the prototype among the neuropsychiatric disorders that fall under the term Hepatic Encephalopathies. Ammonia toxicity is central to the pathophysiology of Portal-systemic encephalopathy, and neuronal ammonia toxicity is modulated by activated astrocytes. The calcium-binding astroglial key protein S100β is released in response to glial activation, and its measurement in serum only recently became possible. Serum S100β was determined by an ultrasensitive ELISA in patients (n=36) with liver cirrhosis and transjugular intrahepatic portosystemic stent-shunt. Subclinical portal-systemic encephalopathy and overt portal-systemic encephalopathy were determined by age-adjusted psychometric tests and clinical staging, respectively. Serum S100β was specifically elevated in the presence of subclinical or early portal-systemic encephalopathy, but not arterial ammonia. S100β levels elevated above a reference value (S100β ≤ 110pg/ml) or the cut off value determined in our group of patients (112pg/ml) predicted subclinical portal-systemic encephalopathy with a specificity and sensitivity of 100 and 56.5%, respectively. Serum S100β was significantly dependent on liver dysfunction (Child-Pugh score), but was more closely related to cognitive impairments than the score. Serum S100β seems to be a promising biochemical surrogate marker for mild cognitive impairments due to portal-systemic encephalopathy.

Quantification of the electroencephalographic theta/alpha ratio for the assessment of portal-systemic encephalopathy following implantation of transjugular intrahepatic portosystemic stent shunt (TIPSS).

The aim of the study was the quantification of metabolically caused electroencephalographic changes of portal-systemic encephalopathy, a prototype of hepatic encephalopathy. We examined 12 patients with liver cirrhosis before and after implantation of a transjugular intrahepatic portosystemic stent shunt (TIPSS) by means of quantitative digital electroencephalography (EEG). One month after TIPSS implantation, all patients showed an increase in the power of the theta frequency band as well as a decrease in the power of the alpha frequency band. To reduce the error variance, we formed the quotient of the relative power of the theta and alpha frequency band. Theta/alpha quotient values over 0.7 indicate a general change of the EEG with a sensitivity of 93% and a specificity of 87%. The results we have to hand indicate a correlation between the albumin concentration and the theta/alpha quotient 1 and 3 months after TIPSS. No significant correlation was revealed with regard to the Child-Pugh score or the liver function parameters cholinesterase, bilirubin, and prothrombin time. Neither the arterial ammonia concentration nor the performance in the psychometric test showed significance in relation to the theta/alpha quotient. Substances with a high albumin bond and potential neurotoxicity may—in the case of lower albumin levels—be absorbed with increased frequency in the CNS and may be responsible for the observed EEG change.

Rimmed vacuoles in facioscapulohumeral muscular dystrophy: a unique ultrastructural feature

Rimmed vacuoles (RV) are a characteristic pathological feature in inclusion body myositis, but may also occur in other neuromuscular disorders, such as distal myopathies, oculopharyngeal myopathy, polymyositis, rigid spine syndrome, congenital myopathies, and some limb girdle muscular dystrophies, as well as in various neurogenic diseases. We describe a patient with RV in familial facioscapulohumeral muscular dystrophy (FSHD) associated with an FSHD-typical deletion on chromosome 4q35. Thus, FSHD should be included in the differential diagnosis of neuromuscular disorders with RV.

Late Increase of Serum S100 β Protein Levels in Hamsters after Oral or Intraperitoneal Infection with Scrapie

Following recent reports of elevated serum S100 beta protein (S100 beta) levels in patients with genetic and sporadic Creutzfeldt-Jakob disease and in rodents parenterally infected with scrapie, the suitability of serum S100 beta as a preclinical marker for transmissible spongiform encephalopathies was assessed in time-course studies. Syrian hamsters were orally and intraperitoneally challenged with scrapie and assayed for serum S100 beta levels at various times after infection. Although elevated serum S100 beta levels were consistently observed in terminally ill animals for both routes of infection, the experiments failed to detect significantly increased S100 beta serum concentrations prior to the manifestation of clinical symptoms. Thus, in this animal model, serum S100 beta does not appear to be an appropriate marker for the preclinical detection of scrapie, but it may provide a convenient laboratory aid for the diagnosis of transmissible spongiform encephalopathy in naturally or accidentally infected animals and humans.

Acutely damaged axons are remyelinated in multiple sclerosis and experimental models of demyelination

Remyelination is in the center of new therapies for the treatment of multiple sclerosis to resolve and improve disease symptoms and protect axons from further damage. Although remyelination is considered beneficial in the long term, it is not known, whether this is also the case early in lesion formation. Additionally, the precise timing of acute axonal damage and remyelination has not been assessed so far. To shed light onto the interrelation between axons and the myelin sheath during de‐ and remyelination, we employed cuprizone‐ and focal lysolecithin‐induced demyelination and performed time course experiments assessing the evolution of early and late stage remyelination and axonal damage. We observed damaged axons with signs of remyelination after cuprizone diet cessation and lysolecithin injection. Similar observations were made in early multiple sclerosis lesions. To assess the correlation of remyelination and axonal damage in multiple sclerosis lesions, we took advantage of a cohort of patients with early and late stage remyelinated lesions and assessed the number of APP‐ and SMI32‐ positive damaged axons and the density of SMI31‐positive and silver impregnated preserved axons. Early de‐ and remyelinating lesions did not differ with respect to axonal density and axonal damage, but we observed a lower axonal density in late stage demyelinated multiple sclerosis lesions than in remyelinated multiple sclerosis lesions. Our findings suggest that remyelination may not only be protective over a long period of time, but may play an important role in the immediate axonal recuperation after a demyelinating insult.

Brain iron accumulation in Wilson disease: a post mortem 7 Tesla MRI - histopathological study.

In Wilson disease (WD), T2/T2*‐weighted (T2*w) MRI frequently shows hypointensity in the basal ganglia that is suggestive of paramagnetic deposits. It is currently unknown whether this hypointensity is related to copper or iron deposition. We examined the neuropathological correlates of this MRI pattern, particularly in relation to iron and copper concentrations.

Unusual localization of a choroid plexus papilloma in a 4-year-old female

Choroid plexus papillomas are rare tumors that are confined to areas in which the choroid plexus is normally located. In children, choroid plexus papillomas are predominantly located in the lateral ventricles. Clinically they present with signs of raised intracranial pressure, such as vomiting and increasing head size. Here we report on the clinical, radiologic, and histologic findings of a 4-year-old female who was found to have a tumor in the posterior fossa that had all the histologic hallmarks of a choroid plexus papilloma. This tumor did not originate from the roof of the fourth ventricle as expected but from the ependymal lining covering the median rostral medulla near the pontomedullary junction, a location that so far has not been reported.

Late progression of neurological symptoms and MRI T2 hyperintensities in Parry-Romberg syndrome

We describe a case of a 50-year-old woman who developed drug-resistant status epilepticus with complex partial and secondary generalised seizures. She had suffered from Parry-Romberg syndrome (PRS) for more than 40 years. Right-sided progressive hemifacial atrophy (PHA) had begun at the age of 7 (figure 1A), followed by epilepsy at the age of 14 years. In the past 2–3 years before the latest admission, the patient had developed a progressive left-sided hemiparesis concomitant with an increase of T2-hyperintensities in the white matter of the right hemisphere, ipsilateral to the PHA (B–D). Moreover, MRI scans illustrated ipsilateral cerebral atrophy (B–D). Blood-sensitive axial imaging revealed evidence of microhaemorrhages or microcalcifications in the right hemisphere (E). Cerebral atrophy was accompanied by contralateral cerebellar atrophy (F). Intrathecal IgG-synthesis as well …