Healthier rhythm, healthier brain? Integrity of circadian melatonin and temperature rhythms relates to the clinical state of brain-injured patients.

BACKGROUND: Healthy circadian rhythmicity has been suggested to relate to a better state of brain-injured patients and to support the emergence of consciousness in patient groups characterized by a relative instability thereof such as patients with disorders of consciousness (DOC). METHODS: Going beyond earlier studies, a systems-level perspective was adopted and, using multilevel modelling, the joint predictive value of three indices of circadian rhythm integrity derived from skin temperature variations, melatoninsulfate secretion, and physical activity (wrist actigraphy) patterns was evaluated for the behaviourally assessed state [Coma Recovery Scale - Revised (CRS-R) score] of DOC patients [13 unresponsive wakefulness syndrome; seven minimally conscious (exit) state]. Additionally, it was assessed in a subset of 16 patients whether patients' behavioural repertoire (CRS-R score) varied (i) with time of day or (ii) offset from the body temperature maximum (BTmax ), i.e. when cognitive performance is expected to peak. RESULTS: The results reveal that better integrity of circadian melatoninsulfate and temperature rhythms relate to a richer behavioural repertoire. Moreover, higher CRS-R scores are, by trend, related to assessments taking place at a later daytime or deviating less from the pre-specified time of occurrence of BTmax . CONCLUSIONS: In conclusion, the results suggest that therapeutic approaches aimed at improving circadian rhythms in brain-injured patients are promising and should be implemented in hospitals or nursing homes. Beyond this, it might be helpful to schedule diagnostic procedures and therapies around the (pre-assessed) BTmax (≈4 pm in healthy individuals) as this is when patients should be most responsive.

Fatal EBV infection and variable clinical manifestations in an XLP-1 pedigree - rapid diagnosis of primary immunodeficiencies may save lives.

Two related boys who died from fulminant infectious mononucleosis were diagnosed with X-linked lymphoproliferative disease type 1 (XLP-1). Family screening (n=17) identified 6 female mutation carriers and 2 more XLP-1 patients in whom, despite recurrent infections, agammaglobulinemia, and Hodgkin's Disease, the genetic basis had been unknown; demonstrating that awareness and early genetic testing are crucial to reveal underlying primary immunodeficiencies and improve outcome. Furthermore, XLP should be included routinely in the differential diagnosis of severe hypogammaglobulinemia and/or lymphoma in males.

Case of Paracoccus yeei infection documented in a transplanted heart.

After a successful cardiac transplantation, routine endomyocardial biopsies showed severe infiltrates comparable with myocarditis. Polymerase chain reaction analysis of native myocardial samples revealed infection with Paracoccus yeei, and the clinical condition of the patient deteriorated. After administration of ciprofloxacin, his clinical condition improved, and further biopsies showed no infiltrates in the cardiac specimens. To our knowledge this is the first documented case of P. yeei infection in a heart transplant patient.

Histopathological prognostic factors in medulloblastoma: high expression of survivin is related to unfavourable outcome.

Standard postoperative treatment of medulloblastoma consists of craniospinal irradiation and chemotherapy. Currently, only clinical factors are used for therapy stratification. To optimise treatment and patient outcome, biological prognostic markers are needed. In the present study we tested the prognostic influence of four histopathological parameters considered in recent publications as prognostic factors in medulloblastoma. We analysed a series of 82 Austrian medulloblastoma patients who were treated according to the consecutive HIT protocols for medulloblastoma conducted by the German Society of Paediatric Haematology and Oncology. Histological subtype and immunohistochemical expression of erbB-2, TRKC, and survivin were determined on paraffin embedded tumour tissue and correlated with patient outcome. Statistical analysis showed a significant correlation of high expression levels of survivin with decreased survival. None of the other investigated histopathological factors correlated significantly with patient outcome. Our data indicate that high survivin expression is related to unfavourable clinical outcome in medulloblastoma patients.

Rare fatal vascular complication of transsphenoidal surgery.

We report the case of a 61-year-old man, who underwent transsphenoidal surgery for a pituitary macroadenoma. The presence of tough fibrous septa dividing the tumour permitted only a partial resection. Progressive loss of consciousness soon after surgery occurred, an emergency CT scan showed no evidence of haemorrhage. Twenty hours later, MRI revealed compression of both internal carotid arteries with arrest of arterial flow resulting in stroke by an enlarged haemorrhagic mass consistent with a pituitary apoplexy. On the second postoperative day, the patient died as a result of this extensive stroke. The mechanisms of this rare complication after transsphenoidal surgery are theorized and the sensitivity of imaging methods is discussed.

[A clinico-pathological case report of necrotizing ulcerating keratopathy due to topical anaesthetic abuse]. / Nekrotisierende ulzerierende Keratopathie nach Lokalanästhetikamissbrauch Ein klinisch-pathologischer Fallbericht.

BACKGROUND: Topical anesthetic abuse is rare, but difficult to diagnose since most patients deny its use and the clinical changes are very similar to other corneal diseases. CASE REPORT: A 45-year-old medical doctor with a 30-year history of soft contact lens wear and recurrent corneal erosion was admitted to our clinic with a ring-shaped keratitis and intense ocular pain. A corneal smear was negative for bacterial infections and acanthamoeba but the contact lens box contained a few dead acanthamoeba and many cocci. Due to the clinical findings and the acanthamoeba found in the contact lens box acanthamoeba keratitis was diagnosed and treatment with gentamycin, pentamidine isethionat (Brolene((R))) and hexamidine (Desomedine((R))) was started. The clinical appearance did not change for 6 weeks after onset of treatment and a perforating corneal transplantation was performed for pain relief and visual rehabilitation. An iris ectropion lacking iris motility and dense cataract developed within 5 weeks and the patient admitted on direct questioning to having taken topical anesthetic (oxybuprocain) by self-medication. The histological investigation revealed few inflammatory cells. The epithelium was largely missing and few vital cells could be found in the stroma and the endothelial cell layer. Acanthamoeba could not be detected in the tissue. CONCLUSION: Topical anesthetic abuse can mimic different corneal diseases and be difficult to diagnose if the patient denies its use. In cases of keratitis with no response to treatment and strong ocular pain, topical anesthetic abuse should be considered.

[Therapy of neurotrophic keratopathy in trigeminal schwannoma with radiosurgery]. / Therapie einer neurotrophen Keratopathie bei Trigeminusschwannom mittels Radiochirurgie.

BACKGROUND: We present a patient with neurotrophic keratopathy due to a trigeminal nerve neurinoma, who was successfully treated by radiosurgery. PATIENT: A patient was referred to us with recurrent corneal erosions of unknown origin in his left eye. In addition, he suffered from mild hypoesthesia in the distribution of the first branch of the trigeminal nerve. He was started on topical lubricants (hyaluronic acid 0.5%) and antibiotic ointments (gentamycin), but since no corneal healing occurred, a soft contact lens was applied. The patient developed severe corneal neovascularization within four weeks and the contact lens had to be removed. Three months later an MRI scan was performed, which showed an intracranial tumor originating from the first branch of the trigeminal nerve. Neurinoma of the trigeminal nerve was suspected, and this presumed diagnosis was confirmed by fine needle biopsy. The patient underwent radiosurgery seven weeks later. The epithelium closed, the cornea recovered and stayed stable until the last examination 18 months after radiosurgery. CONCLUSION: Radiosurgery is a promising alternative to conventional microsurgery in cases of neurinomas of the trigeminal nerve including neurotrophic keratopathy, to keep or restore vision.

Hepatic veno-occlusive disease in two patients with relapsed acute myeloid leukemia treated with anti-CD33 calicheamicin (CMA-676) immunoconjugate.

Monoclonal antibodies recognizing hematopoietic antigens are increasingly being used to target therapy directly at leukemic cells, with the aim of achieving sustained remission with little systemic toxicity. Administration of anti-CD33 calicheamicin immunoconjugate is commonly regarded as being safe, with only moderate systemic non-hematological side effects. We report on two cases of hepatic veno-occlusive disease in heavily pretreated patients presenting with relapsed acute myeloid leukemia (AML). Since significant liver toxicity prevented further specific therapy in both patients, we recommend that antibody therapy with anti-CD33 immunoconjugate should be applied with caution in patients presenting with risk factors for the development of hepatic veno-occlusive disease.