Faculty Bibliography

Ludwig Robert Muller, MD, professor of internal medicine, born in 1870 in Augsburg, Bavaria, studied medicine from 1890 to 1893 in various European cities and specialized in pathology and bacteriology. In 1895, he joined A. Strumpell, one of Germany's outstanding internists and neurologists, in Erlangen, Germany. Henceforth, Muller focused on the autonomic nervous system. In his 1898 Habilitation, a thesis required to join the academic faculty, which he entitled Anatomy and pathology of the lower spinal cord, he presented studies on the autonomic innervation of the bladder and colon. Based on animal studies, he continued to publish essential findings on the autonomic innervation of heart, lungs, and gastrointestinal tract. Muller was the first to report afferent pathways from internal organs to the brain. His book The vegetative nervous system was first published in 1920. In 1931, he wrote the book Lebensnerven und Lebenstriebe (Life nerves and life instincts). Many of his papers dealt with the regulation of thirst, hunger and sleep. He was Chairman of Internal Medicine in Wurzburg, Germany, from 1914 to 1920, and also in Erlangen as Strumpell's successor from 1920 to 1936. The broad scope of Muller's publications makes him one of the important pioneers of autonomic nervous system research

The prevalence of patent foramen ovale (PFO) in healthy individuals is estimated to be about 25% and is elevated to 60% in young patients with kryptogenetic stroke. Pathophysiologically during unvoluntary Valsalva manoeuvres a paradoxical embolism from the venous to the arterial system often occurs. To date, transesophageal echocardiography (TEE) was considered to be the most sensitive way to detect PFO. TEE, however, is semiinvasive, and there are a number of serious complications such as bleeding, hypoxia, bronchospasm, cardiac arrhythmias, bacteremia and sudden cardiac arrest. Transcranial Doppler sonography of the middle cerebral artery during contrast injection [Echovist (c-TCD)] has recently been proposed as an alternative method for the detection of PFO. In a PFO-positive case the typical Doppler wave spectrum is overlapped by high intensity transient signals (HITS) which are caused by the contrast bubbles in the blood stream. However, in the literature and in our own experience there are single cases with false negative results in TEE or in c-TCD. Both methods have a sensitivity of approximately 90% and a specifity of 100%. TEE and TCD-Echovist, used separately, have the small risk of false negative result. Combined use of both methods, however, increases the PFO detection rate. $$:

We present a single case study on neurovascular dopamine effect in a patient with a circumscribed isolated hemodynamic relevant stenosis of the left intracranial internal carotid artery. After percutaneous transluminal angioplasty, angiography showed a restenosis and spasm. To improve cardiac output and to prevent hemodynamic reinfarction continously dopamine (4-7 mu g/kg body weight/min) was infused. Transcranial Doppler sonography (TCD) of the affected left middle cerebral artery (MCA) revealed a constant mean flow velocity (MFV) of 70 cm/sec despite hemodynamic changes due to dopamine. The Pulsatility Index (PI) was constantly low (0.4). suggesting a maximal vasodilation of the ipsilateral resistance vessels. In contrast, during dopamine infusion the MFV of the health!: right side increased from 42 cm/sec to 56 cm/sec and the PI decreased from 0.95 to 0.84. These recordings suggest that cerebral blood supply is augmented by dopamine infusion: firstly, due to an improved cardiac output and secondly, due to slight vasodilation of the cerebral resistance vessels. $$:

Paraneoplastic syndromes of the skeletal muscles as well as of the peripheral and central nervous system are relatively seldom. Typical, disorders are the dermatomyositis, the Lamwbert-Eaton-Syndrome, the subacute sensory neuropathy Denny-Brown, the paraneoplastic sensorimotor polyneuropathy. the subacute necrotizing myelopathy, the spinocerebellar degeneration, the subacute cerebellar degeneration and the encephalomyeloradiculitis with the subtypes bulbar encephalitis, limbic encephalitis and cerebellitis. In some of these disorders tissue-specific antibodies could be observed. This contributions gives an overview on 67 (out of 19.681) patients (0.34%) of our department, regarding the types of the p.s., the interval between the onset of p.s. and the diagnosis of the neoplasms. and the type of tumors accompanying the p.s. The hypotheses explaining the pathogenesis of the p.s., the epidemiology, symptomatology. diagnosis, differential diagnosis and therapeutic possibilities of the various p.s. are discussed and the own data compared with those of the literature. $$:

TCD during ergometer exercise is a new method to evaluate the myogenic mechanism of cerebrovascular autoregulation. Twelve healthy subjects (4 f; 8 m; mean age 33.2 +/- 18.4 years) were investigated by TCD at rest and during ergometer exercise. The Resistance Index (RI) as a measure of vascular resistance was calculated by analysis of the Doppler wave spectrum. The increase of blood pressure (RRsyst. at rest = 118 +/- 7 mmHg; RRsyst. during exercise = 140 +/- 11 mmHg; p ? 0.0001) resulted in significant elevation of RI (RI at rest = 0.55 +/- 0.06; RI during exercise = 0.61 +/- 0.05; p = 0.0111). This phenomen is considered physiological and indicates an intact myogenic mechanism of cerebrovascular autoregulation. By measuring the end-tidal pCO(2) the metabolic autoregulative mechanism could be determined. In ten cases (patients with headache under exercise; patients with migraine and tension type headache; patients under medication of antiepileptic drugs and sympathetic blockers; patient with arterial hypertension; patient with polyneuropathy and autonomic disorder) we demonstrate the clinical relevance of the test. $$:

Hereditary demyelinating peripheral neuropathies consist of a heterogeneous group of genetic disorders that includes hereditary neuropathy with liability to pressure palsies (HNPP), Charcot-Marie-Tooth disease (CMT), Dejerine-Sottas syndrome (DSS), and congenital hypomyelination (CH). The clinical classification of these neuropathies into discrete categories can sometimes be difficult because there can be both clinical and pathologic variation and overlap between these disorders. We have identified five novel mutations in the myelin protein zero (MPZ) gene, encoding the major structural protein (P0) of peripheral nerve myelin, in patients with either CMT1B, DSS, or CH. This finding suggests that these disorders may not be distinct pathophysiologic entities, but rather represent a spectrum of related 'myelinopathies' due to an underlying defect in myelination. Furthermore, we hypothesize the differences in clinical severity seen with mutations in MPZ are related to the type of mutation and its subsequent effect on protein function (i.e., loss of function versus dominant negative)

To evaluate risk factors effecting course and prognosis of neurological intensive care (ICU) patients with special respect to age, 422 patients (235 male, 187 female, mean age 56.7 years, standard deviation +/- 18.8 years) admitted to the ICU of the Department of Neurology, University Erlangen-Nurnberg, were retrospectively studied. The status at the time of ICU discharge was compared to that assessed 18-30 months later using the Barthel-Index, a five grade scale of independence, and the Glasgow Outcome Scale. At the time of reexamination, 203 of the 422 patients (48.2%) were still alive. The fatality rate increased with age. However, approximately 70% of the patients above the age of 70 years were still alive two years after ICU treatment with the majority of patients describing their life as satisfying. Multivariate analysis demonstrated that age by itself does not determine the course of disease. Age affects the prognosis only in combination with other variables such as preexisting diseases (e.g. stroke, carotid surgery, occlusive arterial disease), secondary complications (e. g. pneumonia), and specific ICU treatment (e.g. mechanical ventilation, nasogastric tube), and the patient's state at the time of ICU discharge (bedriddenness, aphasia, dementia)

A retrospective study over four years was performed reviewing the records of 1195 patients suffering from peripheral polyneuropathy without entrapment neuropathies, 613 patients over 60 years of age were compared with 582 patients under 60. Neurological diagnosis was made on the basis of personal and familyhistory, clinical examination, laboratory parameters, electrophysiology and in some cases by sural nerve biopsy, While diabetes was the most frequent etiology in both groups, it was more common in the old-age group (46.5% vs. 32.5%). Clinical manifestation of diabetic neuropathy did not differ. While alcoholism was not a major cause of late life polyneuropathy (2.62 vs. 15.5%), paraneoplastic neuropathy was somewhat more common in late life (3.42 vs, 2.4%) although this was not statistically significant. Paraproteinemic neuropathy as the only cause of neuropathy was found solely in the old-age group (0.8%). The percentage of cryptogenetic neuropathies was higher in late life (17.6% vs. 12.7%; p<0.05) with only the outpatients showing a statistically significant difference (p<0.05). From these findings, we concluded that there is a distinct etiological spectrum of neuropathies in late life, many with treatable causes, The higher percentage of cryptogenetic neuropathies in the elderly may be explained by a nonspecific neuropathy occurring in late life due to normal aging processes in the peripheral nerve. $$: