Christoph Spitzer

Peripheral but not central axotomy induces changes in Janus kinases (JAK) and signal transducers and activators of transcription (STAT)

Nerve injury leads to the release of a number of cytokines which have been shown to play an important role in cellular activation after peripheral nerve injury. The members of the signal transducer and activator of transcription (STAT) gene family are the main mediators in the signal transduction pathway of cytokines. After phosphorylation, STAT proteins are transported into the nucleus and exhibit transcriptional activity. Following axotomy in rat regenerating facial and hypoglossal neurons, a transient increase of mRNA for JAK2, JAK3, STAT1, STAT3 and STAT5 was detected using in situ hybridization and semi‐quantitative polymerase chain reaction (PCR). Of the investigated STAT molecules, only STAT3 protein was significantly increased. In addition, activation of STAT3 by phosphorylation on position Tyr705 and enhanced nuclear translocation was found within 3 h in neurons and after 1 day in astrocytes. Unexpectedly, STAT3 tyrosine phosphorylation was obvious for more than 3 months. In contrast, none of these changes was found in response to axotomy of non‐regenerating Clarkes nucleus neurons, although all the investigated models express c‐Jun and growth‐associated protein‐43 (GAP‐43) in response to axonal injury. Increased expression of Janus kinase (JAK) and STAT molecules after peripheral nerve transection suggests changes in the responsiveness of the neurons to signalling molecules. STAT3 as a transcription factor, which is expressed early and is activated persistently until the time of reinnervation, might be involved in the switch from the physiological gene expression to an ‘alternative program’ activated only after peripheral nerve injury.

Surveillance of nosocomial infections in a neurologic intensive care unit.

OBJECTIVE To assess data on the epidemiology of nosocomial infection (NI) among neurologic intensive care patients. DESIGN Prospective periodic surveillance study. SETTING An 8-bed neurologic intensive care unit (ICU). PATIENTS All those admitted for more than 24 hours during five 3-month periods between January 1999 and March 2003. METHODS Standardized surveillance within the German infection surveillance system. RESULTS Three hundred thirty-eight patients with a total of 2,867 patient-days and a mean length of stay of 8.5 days were enrolled during the 15-month study period. A total of 71 NIs were identified among 52 patients. Urinary tract infections (UTIs) were the most frequent NI (36.6%), followed by pneumonia (29.6%) and bloodstream infections (BSIs) (15.5%). The overall incidence and incidence density of NIs were 21.0 per 100 patients and 24.8 per 1,000 patient-days, respectively. Incidence densities were 9.8 UTIs per 1,000 urinary catheter-days (CI95, 6.4-14.4), 5.6 BSIs per 1,000 central venous catheter-days (CI9s, 2.8-10.0), and 12.8 cases of pneumonia per 1,000 ventilation-days (Cl95, 8.0-19.7). Device-associated UTI and pneumonia rates were in the upper range of national and international reference data for medical ICUs, despite the intensive infection control and prevention program in operation in the hospital. CONCLUSION Neurologic intensive care patients have relatively high rates of device-associated nosocomial pneumonia and UTI. For a valid comparison of surveillance data and implementation of targeted prevention strategies, we would strongly recommend provision of national benchmarks for the neurologic ICU setting.

Isolated hypoglossal nerve palsy caused by carotid artery dissection the necessity of MRI for diagnosis.

Sirs: XIIth nerve palsy has a variety of causes such as malignant tumors in the base of the skull, trauma, neurinomas, meningeosis carcinoma, surgery of the carotid artery and infectious diseases [2, 4, 12]. Sometimes, no reason can be found despite extensive investigations. These are therefore cases categorized as idiopathic palsies. Only in recent years has it been recognized that hypoglossal nerve palsy can rarely be caused by spontaneous internal carotid artery (ICA) dissection. In most cases these patients present with additional symptoms such as ipsilateral Horner’s syndrome or lesions of other lower cranial nerves [1, 5, 11]. ICA dissection must therefore be included in the differential diagnosis of isolated XIIth nerve palsy and should be assessed by magnetic resonance imaging (MRI) as is demonstrated by our case. A 39-year-old engineer had suffered from persistent pain at the left mandibular angle for several weeks. He could not remember any initiating trauma. Approximately 10 days before admission the patient had experienced difficulty in moving his tongue. Clinical examination revealed a left hypoglossal nerve palsy: The tongue deviated to the left side when protruded, was positioned to the right when resting in the oral cavity and tongue movements were impared. No other neurological deficit could be observed; in particular, no other cranial nerve affection or Horner’s syndrome was evident. Computed tomography of the brain and base of the skull did not reveal any abnormality, in particular, the hypoglossal canal was inconspicuous. Routine analysis of the cerebrospinal fluid and blood was normal. MRI (Philips Gyroscan 0,5T) revealed a circumscribed dissection of the left ICA extending for approximately 20 mm from the distal cervical into the proximal petrosal segment (Figure). The hyperintense signal in the T2weighted images and in the T1weighted images with fat suppression clearly indicated an intramural hematoma surrounding the artery with a semilunar shape. Its maximum extension was on the dorso-lateral surface. There was no LETTER TO THE EDITORS

Regulation of stearoyl-CoA desaturase-1 after central and peripheral nerve lesions.

BackgroundInterruption of mature axons activates a cascade of events in neuronal cell bodies which leads to various outcomes from functional regeneration in the PNS to the failure of any significant regeneration in the CNS. One factor which seems to play an important role in the molecular programs after axotomy is the stearoyl Coenzyme A-desaturase-1 (SCD-1). This enzyme is needed for the conversion of stearate into oleate. Beside its role in membrane synthesis, oleate could act as a neurotrophic factor, involved in signal transduction pathways via activation of protein kinases C.ResultsIn situ hybridization and immunohistochemistry demonstrated a strong up-regulation of SCD at mRNA and protein level in regenerating neurons of the rat facial nucleus whereas non-regenerating Clarkes and Red nucleus neurons did not show an induction of this gene.ConclusionThis differential expression points to a functionally significant role for the SCD-1 in the process of regeneration.

Isolierte Hirnnervenausfälle bei Karotisdissektionen

ZusammenfassungEin isolierter Hirnnervenausfall kann eine Vielzahl verschiedener Ursachen haben wie z.B.eine Hirnstammischämie, eine Ischämie der Vasa nervorum bei Diabetes mellitus, Subarachnoidalblutungen, infektiöse und nichtinfektiöse Meningitiden, Metastasen im Bereich der Schädelbasis, des Hales oder des oberen Mediastinums, enzündliche Erkrankungen wie beispielsweise eine Sarkoidose oder ein Tolosa-Hunt-Syndrom,Prozesse im Sinus cavernosus und Aortenaneurysmen. Die Karotisdissektion ist eine seltene Ätiologie eines isolierten Hirnnervenausfalls-wir stellen hierzu zwei Fallbeispiele vor und geben einen Überblick über die aktuelle Literatur. Eine fehlende Behandlung hat möglicherweise fatale Folgen für den Patienten. Daher sollte die Karotisdissektion in die differenzialdiagnostischenÜberlegungen miteinbezogen werden.Der Nachweis sollte mittels Farbduplexsonographie und/oder MR-Tomographie erfolgen.SummaryCranial nerve palsy has a variety of causes such as cerebral ischemia, nerve ischemia in diabetes, infectious and noninfectious meningitis, subarachnoid hemorrhage, malignant tumors of the skull base, neck, or upper mediastinum, aortic aneurysm, surgery of the thyroid,and many more.We report two cases of spontaneous carotid dissections leading to cranial nerve palsies, which is an uncommon cause of isolated cranial nerve palsies.ICA dissection must therefore be included in the differential diagnosis of lower cranial nerve palsy and should be assessed by duplex ultrasound and MRI as is demonstrated in our cases.