Primary localized rectal/pararectal gastrointestinal stromal tumors: results of surgical and multimodal therapy from the French Sarcoma group.

BACKGROUND: Rectal and pararectal gastrointestinal stromal tumors (GISTs) are rare. The optimal management strategy for primary localized GISTs remains poorly defined. METHODS: We conducted a retrospective analysis of 41 patients with localized rectal or pararectal GISTs treated between 1991 and 2011 in 13 French Sarcoma Group centers. RESULTS: Of 12 patients who received preoperative imatinib therapy for a median duration of 7 (2-12) months, 8 experienced a partial response, 3 had stable disease, and 1 had a complete response. Thirty and 11 patients underwent function-sparing conservative surgery and abdominoperineal resection, respectively. Tumor resections were mostly R0 and R1 in 35 patients. Tumor rupture occurred in 12 patients. Eleven patients received postoperative imatinib with a median follow-up of 59 (2.4-186) months. The median time to disease relapse was 36 (9.8-62) months. The 5-year overall survival rate was 86.5%. Twenty patients developed local recurrence after surgery alone, two developed recurrence after resection combined with preoperative and/or postoperative imatinib, and eight developed metastases. In univariate analysis, the mitotic index (≤5) and tumor size (≤5 cm) were associated with a significantly decreased risk of local relapse. Perioperative imatinib was associated with a significantly reduced risk of overall relapse and local relapse. CONCLUSIONS: Perioperative imatinib therapy was associated with improved disease-free survival. Preoperative imatinib was effective. Tumor shrinkage has a clear benefit for local excision in terms of feasibility and function preservation. Given the complexity of rectal GISTs, referral of patients with this rare disease to expert centers to undergo a multidisciplinary approach is recommended.

Functional and histopathological identification of the respiratory failure in a DMSXL transgenic mouse model of myotonic dystrophy.

Acute and chronic respiratory failure is one of the major and potentially life-threatening features in individuals with myotonic dystrophy type 1 (DM1). Despite several clinical demonstrations showing respiratory problems in DM1 patients, the mechanisms are still not completely understood. This study was designed to investigate whether the DMSXL transgenic mouse model for DM1 exhibits respiratory disorders and, if so, to identify the pathological changes underlying these respiratory problems. Using pressure plethysmography, we assessed the breathing function in control mice and DMSXL mice generated after large expansions of the CTG repeat in successive generations of DM1 transgenic mice. Statistical analysis of breathing function measurements revealed a significant decrease in the most relevant respiratory parameters in DMSXL mice, indicating impaired respiratory function. Histological and morphometric analysis showed pathological changes in diaphragmatic muscle of DMSXL mice, characterized by an increase in the percentage of type I muscle fibers, the presence of central nuclei, partial denervation of end-plates (EPs) and a significant reduction in their size, shape complexity and density of acetylcholine receptors, all of which reflect a possible breakdown in communication between the diaphragmatic muscles fibers and the nerve terminals. Diaphragm muscle abnormalities were accompanied by an accumulation of mutant DMPK RNA foci in muscle fiber nuclei. Moreover, in DMSXL mice, the unmyelinated phrenic afferents are significantly lower. Also in these mice, significant neuronopathy was not detected in either cervical phrenic motor neurons or brainstem respiratory neurons. Because EPs are involved in the transmission of action potentials and the unmyelinated phrenic afferents exert a modulating influence on the respiratory drive, the pathological alterations affecting these structures might underlie the respiratory impairment detected in DMSXL mice. Understanding mechanisms of respiratory deficiency should guide pharmaceutical and clinical research towards better therapy for the respiratory deficits associated with DM1.

Immunogold Detection of L-glutamate and D-serine in Small Synaptic-Like Microvesicles in Adult Hippocampal Astrocytes.

Glutamate and the N-methyl-D-aspartate receptor ligand D-serine are putative gliotransmitters. Here, we show by immunogold cytochemistry of the adult hippocampus that glutamate and D-serine accumulate in synaptic-like microvesicles (SLMVs) in the perisynaptic processes of astrocytes. The estimated concentration of fixed glutamate in the astrocytic SLMVs is comparable to that in synaptic vesicles of excitatory nerve terminals (∼45 and ∼55 mM, respectively), whereas the D-serine level is about 6 mM. The vesicles are organized in small spaced clusters located near the astrocytic plasma membrane. Endoplasmic reticulum is regularly found in close vicinity to SLMVs, suggesting that astrocytes contain functional nanodomains, where a local Ca(2+) increase can trigger release of glutamate and/or D-serine.

Tracking the source of cerebellar epilepsy: hemifacial seizures associated with cerebellar cortical dysplasia.

Traditionally, subcortical structures such as the cerebellum are supposed to exert a modulatory effect on epileptic seizures, rather than being the primary seizure generator. We report a 14-month old girl presenting, since birth, with seizures symptomatic of a right cerebellar dysplasia, manifested as paroxystic contralateral hemifacial spasm and ipsilateral facial weakness. Multimodal imaging was used to investigate both anatomical landmarks related to the cerebellar lesion and mechanisms underlying seizure generation. Electric source imaging (ESI) supported the hypothesis of a right cerebellar epileptogenic generator in concordance with nuclear imaging findings; subsequently validated by intra-operative intralesional recordings. Diffusion spectrum imaging-related tractography (DSI) showed severe cerebellar structural abnormalities confirmed by histological examination. We suggest that hemispheric cerebellar lesions in cases like this are likely to cause epilepsy via an effect on the facial nuclei through ipsilateral and contralateral aberrant connections.

Survey on current practices for neurological prognostication after cardiac arrest.

PURPOSE: To investigate current practices and timing of neurological prognostication in comatose cardiac arrest patients. METHODS: An anonymous questionnaire was distributed to the 8000 members of the European Society of Intensive Care Medicine during September and October 2012. The survey had 27 questions divided into three categories: background data, clinical data, decision-making and consequences. RESULTS: A total of 1025 respondents (13%) answered the survey with complete forms in more than 90%. Twenty per cent of respondents practiced outside of Europe. Overall, 22% answered that they had national recommendations, with the highest percentage in the Netherlands (>80%). Eighty-nine per cent used induced hypothermia (32-34 °C) for comatose cardiac arrest patients, while 11% did not. Twenty per cent had separate prognostication protocols for hypothermia patients. Seventy-nine per cent recognized that neurological examination alone is not enough to predict outcome and a similar number (76%) used additional methods. Intermittent electroencephalography (EEG), brain computed tomography (CT) scan and evoked potentials (EP) were considered most useful. Poor prognosis was defined as cerebral performance category (CPC) 3-5 (58%) or CPC 4-5 (39%) or other (3%). When prognosis was considered poor, 73% would actively withdraw intensive care while 20% would not and 7% were uncertain. CONCLUSION: National recommendations for neurological prognostication after cardiac arrest are uncommon and only one physician out of five uses a separate protocol for hypothermia treated patients. A neurological examination alone was considered insufficient to predict outcome in comatose patients and most respondents advocated a multimodal approach: EEG, brain CT and EP were considered most useful. Uncertainty regarding neurological prognostication and decisions on level of care was substantial.

International survey of acute stroke imaging used to make revascularization treatment decisions.

BACKGROUND: To assess the differences across continental regions in terms of stroke imaging obtained for making acute revascularization therapy decisions, and to identify obstacles to participating in randomized trials involving multimodal imaging. METHODS: STroke Imaging Repository (STIR) and Virtual International Stroke Trials Archive (VISTA)-Imaging circulated an online survey through its website, through the websites of national professional societies from multiple countries as well as through email distribution lists from STIR and the above mentioned societies. RESULTS: We received responses from 223 centers (2 from Africa, 38 from Asia, 10 from Australia, 101 from Europe, 4 from Middle East, 55 from North America, 13 from South America). In combination, the sites surveyed administered acute revascularization therapy to a total of 25,326 acute stroke patients in 2012. Seventy-three percent of these patients received intravenous (i.v.) tissue plasminogen activator (tPA), and 27%, endovascular therapy. Vascular imaging was routinely obtained in 79% (152/193) of sites for endovascular therapy decisions, and also as part of standard IV tPA treatment decisions at 46% (92/198) of sites. Modality, availability and use of acute vascular and perfusion imaging before revascularization varied substantially between geographical areas. The main obstacles to participate in randomized trials involving multimodal imaging included: mainly insufficient research support and staff (50%, 79/158) and infrequent use of multimodal imaging (27%, 43/158) . CONCLUSION: There were significant variations among sites and geographical areas in terms of stroke imaging work-up used tomake decisions both for intravenous and endovascular revascularization. Clinical trials using advanced imaging as a selection tool for acute revascularization therapy should address the need for additional resources and technical support, and take into consideration the lack of routine use of such techniques in trial planning.