Peripapillary retinal nerve fibre layer thinning rate as a biomarker discriminating stable and progressing relapsing-remitting multiple sclerosis.

BACKGROUND AND PURPOSE: Peripapillary retinal nerve fibre layer (pRNFL) thickness is a strong candidate as a biomarker of axonal degeneration in multiple sclerosis (MS). The aim was to determine a cut-off value of pRNFL thinning rates in relapsing-remitting MS (RRMS) to discriminate between stable and progressing patients. METHODS: In this 3-year prospective longitudinal study on 141 RRMS patients, annual pRNFL thinning rates (aLpRNFL) were determined by individual linear regression models. The best possible cut-off value discriminating clinically progressing (physical progression or cognitive decline) and stable patients was defined by receiver operating characteristic analysis. Cut-off values were validated using a multivariate logistic regression model. RESULTS: Average aLpRNFL in progressing patients (2.4 µm, SD 2.1) was significantly higher compared to stable patients (0.5 µm, SD 1.2, P < 0.001). At a predefined specificity of 90%, aLpRNFL >1.5 µm was able to distinguish between stable and progressing RRMS with a sensitivity of 76.1%. aLpRNFL >1.5 µm was associated with a 15-fold increased risk of clinically progressing MS (P < 0.001). CONCLUSIONS: A cut-off of aLpRNFL discriminating clinically progressing and stable RRMS was identified. After validation in independent cohorts, this cut-off could be used as a biomarker of axonal degeneration supporting disease monitoring in daily clinical routine.

[Consensus statement "Dementia 2010" of the Austrian Alzheimer Society]. / Konsensusstatement "Demenz 2010" der Osterreichischen Alzheimer Gesellschaft.

The Austrian Alzheimer Society developed evidence-based guidelines based on a systematic literature search and criteria-guided assessment with subsequent transparent determination of grades of clinical recommendation. The authors evaluated currently available therapeutic approaches for the most common forms of dementia and focused on diagnosis and pharmacological intervention, taking into consideration the situation in Austria. The purpose of these guidelines is the rational and cost-effective use of diagnostic and therapeutic measures in dementing illnesses. Users are physicians and all other providers of care for patients with dementia in Austria.

Time course of cerebral blood flow velocity in central nervous system infections. A transcranial Doppler sonography study.

In a 3-year period, 110 patients with central nervous system infections of various causes were examined serially by means of transcranial Doppler sonography. In viral-induced infections, no changes of flow velocity in basal cerebral arteries were seen, whereas in bacterial meningitis, a significant increase of blood flow velocity in the middle cerebral artery was recorded. Its extent was mainly associated with the type of the infectious agent, most frequently observed in pneumococcal meningitis (77%). The increase was up to 100% of the baseline values and was reversible in all cases. All patients were offered full-scale neurointensive care, and all subjects with bacterial meningitis were fully heparinized.

Common subtypes of idiopathic generalized epilepsies: lack of linkage to D20S19 close to candidate loci (EBN1, EEGV1) on chromosome 20.

Hereditary factors play a major role in the etiology of idiopathic generalized epilepsies (IGEs). A trait locus (EBN1) for a rare subtype of IGEs, the benign neonatal familial convulsions, and a susceptibility gene (EEGV1) for the common human low-voltage electroencephalogram have been mapped close together with D20S19 to the chromosomal region 20q13.2. Both loci are potential candidates for the susceptibility to IGE spectra with age-related onset beyond the neonatal period. The present study tested the hypothesis that a putative susceptibility locus linked to D20S19 predisposes to spectra of IGEs with age-related onset from childhood to adolescence. Linkage analyses were conducted in 60 families ascertained through IGE patients with juvenile myoclonic epilepsy, juvenile absence epilepsy or childhood absence epilepsy. Our results provide evidence against linkage of a putative susceptibility gene for four hierarchically broadened IGE spectra with D20S19 assuming tentative single-locus genetic models. The extent of an "exclusion region" (lod scores below-2) varied from 0.5 cM up to 22 cM on either side of D20S19 depending on the trait assumed. These results are contrary to the expectation that a susceptibility gene in vicinity to D20S19 confers a common major gene effect to the expression of IGE spectra with age-related onset from childhood to adolescence.

Polyneuropathies in critically ill patients: a prospective evaluation.

OBJECTIVE: To determine the incidence, severity and course of polyneuropathies in patients with sepsis or systemic inflammatory response syndrome combined with multiple organ failure. DESIGN: Prospective study. SETTING: Division of Intensive Care Medicine of the Department of Anesthesiology and Intensive Care and Intensive Care Unit of the Department of Neurology, University Hospital Innsbruck, Austria. PATIENTS: Twenty-two patients between 23 and 77 years old with sepsis or systemic inflammatory response syndrome combined with multiple organ failure fulfilling strict inclusion and exclusion criteria. INTERVENTIONS: Clinical neurologic examination and electro myography/nerve conduction velocity measurements during the stay on the Intensive Care Unit and 2-3 months later. MEASUREMENTS AND RESULTS: In 9 of the 22 patients signs of polyneuropathy were found at the initial clinical investigation and in 7 patients at the follow-up investigation. Electrophysiologic investigation revealed signs of polyneuropathy in 18 patients initially and in 11 patients 2-3 months later. CONCLUSION: In our patient population the frequency of the development of polyneuropathy was high (81.8%). Electrophysiologic investigation is superior to clinical neurologic examination in the detection of polyneuropathies.

The prognostic significance of coma-rating, duration of anoxia and cardiopulmonary resuscitation in out-of-hospital cardiac arrest.

Early determination of outcome after successful prehospital cardiopulmonary resuscitation (CPR) is a common problem with great ethical, economic, social, and legal consequences. We prospectively investigated 112 adult patients who had been resuscitated after out-of-hospital cardiac arrest (CA). The aim of our study was to determine whether coma rating by the mobile intensive care unit (MICU) is a useful tool for outcome prediction. For neurological assessment the Innsbruck Coma Scale (ICS) was used initially and after return of spontaneous circulation (ROSC) or 20-30 min after the start of CPR, before any sedating drugs were given. The duration of anoxia and CPR were determined with the automatically recorded emergency call protocol of the dispatch centre and the protocol of the MICU. For estimation of cerebral outcome at the time of discharge from hospital we used the Glasgow-Pittsburgh Cerebral Performance Categories (CPC). Restoration of spontaneous circulation was achieved in 42 patients (37%), and 15 (13%) were discharged from hospital. The first coma rating performed immediately at the time of arrival on scene had no significant prognostic value for prediction of neurological outcome (P = 0.204) and survival (P = 0.103). The second coma rating (performed after ROSC or 20-30 min after the start of CPR), however, demonstrated a significant correlation with neurological outcome (P = 0.0000) and survival (P = 0.0000), a correlation which was comparable to both duration of anoxia and duration of CPR. In patients with out-of-hospital cardiac arrest prognostic information could be obtained with the ICS as early as 20-30 min after the start of cardiopulmonary resuscitation.

Hemispheric disconnection in Marchiafava-Bignami disease: clinical, neuropsychological and MRI findings.

We report a single-case study of a patient suffering from Marchiafava-Bignami disease (MBD), a rarely intra vitam diagnosed syndrome with focal demyelination in the corpus callosum, which is usually found in patients with chronic alcohol abuse. Our study explored a variety of motor, sensory and visual functions. Striking features were left apraxia caused by two lesions in the rostral area, and left hemidyslexia related to a large splenial lesion demonstrated by MRI. As symptoms of disconnection may remain undetected clinically, MRI is a most useful tool for the diagnosis of MBD.

Superficial siderosis of the central nervous system: report of three cases and review of the literature.

We present 3 cases and a review of the literature to demonstrate the current state of clinical diagnosis and therapy of superficial siderosis of the central nervous system. Typical symptoms were progressive cerebellar ataxia, spasticity and hearing loss. Repeated subarachnoid hemorrhage was indicated by persistent xanthochromia of the cerebrospinal fluid and confirmed by the presence of erythrophages, siderophages and iron-containing pigments. Deposition of free iron and hemosiderin in pial and subpial structures leads to intoxication of the central nervous system and represents the pathophysiological mechanism of superficial siderosis. Hypointensity of the marginal zones of the central nervous system on T2 weighted MR images indicates an iron-induced susceptibility effect and seems pathognomonic for superficial siderosis. In 39 of the 43 previously described cases superficial siderosis was verified by biopsy or autopsy. Today magnetic resonance imaging enables diagnosis at an early stage of the disease. Therapeutic management requires the elimination of any potential source of bleeding. In patients with unknown etiology no proofed therapy is yet available.

[Polyneuropathy in the critically ill patient--critical illness polyneuropathy]. / Die Polyneuropathie des kritisch kranken Patienten--critical illness polyneuropathy.

Polyneuropathy developing in critically ill patients ("critical illness polyneuropathy"--CIP) is diagnosed with increasing frequency in intensive care units. CIP is an axonal polyneuropathy leading to difficulties in weaning from artificial ventilation and symmetrical flaccid tetraparesis. Pathogenetically CIP is considered to be part of the multiple organ dysfunction syndrome (MODS) in the course of sepsis or systemic inflammatory response syndrome (SIRS). The incidence of CIP in septic patients with MODS ranges from 50% to 70%. Electroneurography (ENG) and electromyography (EMG) are essential diagnostic procedures. The mortality in patients with CIP is higher than in patients without CIP. Depending on the severity of CIP, recovery of neurological function in survivors is usually relatively good.

[Neurologic manifestations of diabetes mellitus: an overview]. / Neurologische Manifestationen des Diabetes mellitus: ein Uberblick.

Neurological manifestations of diabetes mellitus comprise structural changes in both central and peripheral nervous system, as well as functional cerebral disturbances. Macro- and microangiopathy are responsible for the development of cerebrovascular diseases; microangiopathic and metabolic disturbances are considered in the discussion to be responsible for the development of the various forms of diabetic polyneuropathy. Acute metabolic episodes with progressive impairment of consciousness have to be differentiated from structural neurological disorders. As a further point of interest the association between diabetes mellitus and special neurological diseases is mentioned.

[Neurologic symptoms within the scope of endocrine emergencies]. / Neurologische Symptome im Rahmen endokriner Notfälle.

Functional disturbances of the central and peripheral nervous system can be seen in various internal diseases and it is not unusual that neurological symptoms are the first kind of presentation. The tight anatomical and functional junction between neurology and endocrinology predisposes to the development of neurological derangements such as somnolence, coma, seizures, and focal signs following endocrinological emergencies. In spite of modern imaging and laboratory methods, history and clinical examination are still of great importance to establish the correct diagnosis.

[Course and management of tetanus]. / Verlauf und Management des Tetanus.

Within a span of 18 months 4 patients (2 men, 2 women) were admitted with generalized tetanus to our neurological intensive care unit. The "period of onset" ranged from 2 to 14 days. All patients needed artificial ventilation over 17 to 38 days. The clinical course was complicated by gram-negative pneumonia in 3 of the 4 patients. Time of hospitalization ranged between 35 and 60 days. One patient had never been immunized against tetanus. The other 3 had not received a booster dose for over 10 years. All 4 patients survived, 3 of them without sequelae.

Diagnosis of tuberculous meningitis by detection of tuberculostearic acid in cerebrospinal fluid.

Tuberculous meningitis still poses a major diagnostic problem. Recently, several new techniques for rapid diagnosis of tuberculous meningitis have been developed. One of these newer techniques is the detection of mycobacterial fatty acids, using gas chromatography--mass spectroscopy. In this study we evaluated the sensitivity and specificity of this recently reported method in a blind trial. The sensitivity was found to be 100%, specificity only 91%. The number of false positive results limits the value of this test in the primary diagnosis of tuberculous meningitis. Nonetheless, we consider this method to be a valuable tool for establishing the diagnosis in culture-negative patients presenting with signs and symptoms suggestive of tuberculous meningitis.

[Cerebral and spinal nocardia infection. A case report]. / Zerebrale und spinale Nokardieninfektion. Ein Fallbericht.

We report a case of multiple cerebral and spinal abscesses due to Nocardia asteroides in a non-immunocompromised patient. The initial central nervous system manifestation was a sterile meningitis, with secondary development of multiple cerebral and spinal abscesses. Since the location of the abscesses did not allow neurosurgical exploration and the cultures remained negative, the diagnosis was finally established by raised antibody titres to Nocardia asteroides. After specific antibiotic therapy, resolution of the spinal and cerebral abscesses was documented on the basis of serial magnetic resonance tomography and computed tomography controls.

The prognostication of cerebral hypoxia after out-of-hospital cardiac arrest in adults.

Early determination of outcome after out-of-hospital cardiopulmonary resuscitation is a common problem with great ethical, economic, social and legal consequences. Although there has been a fulminant development of emergency medicine during the last three decades, severe cerebral damage sometimes cannot be avoided. For neurological outcome prediction after cardiac arrest clinical neurological signs, electrophysiological examinations, neuroimaging tests, and laboratory parameters in serum and cerebrospinal fluid are used today, nevertheless, there still remains a considerable degree of uncertainty. However, although prognostic criteria which enable the clinician to stop treatment cannot be given at the present time, useful applications of early prognostication after cardiac arrest range from counseling of families, triage decisions, and do-not-resuscitate decisions to future clinical investigations of brain resuscitative measures.

[Several years observation of a Catergen (cyanidanol-3) induced immunohemolysis]. / Mehrjährige Verlaufsbeobachtung einer durch Catergen (Cyanidanol-3) induzierten Immunhämolyse.

A report is presented on repeated severe episodes of cyanidanol-induced immune hemolysis in a 75-year-old woman suffering from chronic active hepatitis. One year after the first hemolytic episode, high titers of anticyanidanol antibodies were still demonstrated in the patient's serum (as well as sensitization of the patient's lymphocytes by the drug). 4 years later virtually no decrease of the antibody titer was found. Further investigations of the patient's serum revealed antibodies against flavonoids with free hydroxyl groups (cyanidanol and rutin). However, no antibodies against flavonoids with derivatized hydroxyl groups (troxerutin, mixture of hydroxy-ethyl-rutin and silibinin) could be demonstrated. Sensitization with flavonoids other than cyanidanol preceding cyanidanol-induced hemolysis has been proposed by others. In this case storage of approximately 75 flavonoid containing preparations in a chemist's shop in the patient's house may have contributed to the astonishing persistence of dry dependent antibodies.

Subarachnoid hemorrhage as presenting feature of isolated neurosarcoidosis.

A 35-year-old man presented with the clinical picture of spontaneous subarachnoid hemorrhage. Four weeks after the first symptoms he noticed blurred vision, and ophthalmological examination detected bitemporal hemianopia. At this time cerebral computed tomography and magnetic resonance imaging showed enlargement of the optic chiasm, and visual evoked potentials revealed delayed latencies. In the cerebrospinal fluid cells and protein content were elevated, and angiotensin-converting enzyme was detectable. Under steroid treatment the patient recovered completely and computed tomography, magnetic resonance imaging, visual evoked potentials, and cerebrospinal fluid findings became normal. Although a great variety of neurological symptoms may occur in neurosarcoidosis, to our knowledge spontaneous subarachnoid hemorrhage as the presenting feature has never been reported before.