Ondine's curse with accompanying trigeminal and glossopharyngeal neuralgia secondary to medullary telangiectasia.

BACKGROUND: Central hypoventilation syndrome ("Ondine's Curse") is an infrequent disorder that can lead to serious acute or chronic health consequences. This syndrome, especially in adults, is rare, and even less frequent in the absence of clear pathogenic lesions on MRI. In addition, we are not aware of any previously reported cases with associated cranial nerve neuralgias. METHODS: We describe a patient with baseline trigeminal and glossopharyngeal neuralgia, admitted with episodes of severe hypoventilatory failure of central origin, consistent with "Ondine's Curse". After evaluation, she was found to have a medullary capillary telangiectasia, thought to be the causative lesion, and which could explain her complete neurologic and hypoventilatory syndrome. The patient was treated with placement of a diaphragmatic pacing system, which has been effective thus far. RESULTS: This case illustrates the need for investigation of centrally mediated apnea, especially when co-occurring cranial nerve neuralgia is present and cardiopulmonary evaluation is negative. It provides an example of capillary telangiectasia as the causative lesion, one that to our knowledge has not been reported before. CONCLUSIONS: Placement of a diaphragmatic pacing system was warranted and became lifesaving as the patient was deemed to be severely incapacitated by chronic ventilatory insufficiency.

Intraventricular hemorrhage volume predicts poor outcomes but not delayed ischemic neurological deficits among patients with ruptured cerebral aneurysms.

BACKGROUND: Intraventricular hemorrhage (IVH) predicts worse outcomes following aneurysmal subarachnoid hemorrhage (SAH). One potential mechanism is that IVH predisposes to the development of delayed ischemic neurological deficits (DINDs). No previous studies have evaluated the association between IVH volume (in milliliters) and subsequent development of DINDs or poor outcomes. OBJECTIVE: To assess the association between the volume of IVH and the subsequent development of DINDs, delayed cerebral infarction, death, and poor neurological outcomes, specifically among patients with concomitant SAH and IVH. METHODS: We performed a cohort study involving 152 consecutive patients with concomitant SAH and IVH. To determine volume of IVH, we used the IVH Score, shown to correlate well with computerized volumetric assessment. To determine the relative quantity of subarachnoid blood, we applied the SAH Sum Score. Multivariate logistic regression was used to adjust for potential confounders. RESULTS: There was no significant association between IVH volume and the development of DINDs or delayed infarction. In contrast, patients with poor neurological outcomes had significantly larger baseline IVH volume (mean, 11.8 mL vs 3.8 mL, P = .001). In the multivariate analysis, IVH volume was an independent predictor of poor outcomes (OR per mL: 1.11 [1.04-1.18]). Patients in the highest quartile for IVH volume were far more likely to progress to poor outcome compared with those in the lowest quartile (OR 4.09 [1.32-12.65]). Interobserver agreement in the determination of IVH Score was moderate to good. CONCLUSIONS: IVH volume is an independent predictor of poor neurological outcomes, even after adjusting for the amount of subarachnoid blood. The pathophysiology of this association does not appear to involve an increased risk of DINDs or delayed infarction. Measures aimed at accelerating IVH clearance, such as intraventricular thrombolysis, merit further evaluation.

A Golgi study of neuronal architecture in a genetic mouse model for Lesch-Nyhan disease.

Lesch-Nyhan disease (LND) is an inherited disorder associated with deficiency of hypoxanthine-guanine phosphoribosyltransferase (HPRT), an enzyme essential for purine recycling. The clinical manifestations of the disorder and several neurochemical studies have pointed towards a defect in the striatum, but histological studies of autopsied brain specimens have not revealed any consistent abnormalities. An HPRT-deficient (HPRT-) mouse that has been produced as a model for the disease also exhibits neurochemical abnormalities of the striatum without obvious histological correlates. In the current studies, Golgi-Cox histochemistry was used to evaluate the fine structure of medium spiny I neurons from the striatum in the HPRT- mice. To determine if any abnormalities might be restricted to striatal neurons, the pyramidal projection neurons of layer 5 of the cerebral cortex were also evaluated. Neurons from both regions demonstrated a normal distribution, orientation, and gross morphology. There was no evidence for an abnormal developmental process or degeneration. However, both regions demonstrated a paucity of neurons with very long dendrites and a reduction in dendritic spines that depended upon the distance from the cell body. These findings demonstrate that HPRT deficiency is associated with changes in neuronal architecture in the HPRT- mice. Similar abnormalities in the LND brain could underlie some of the clinical manifestations.

Specific localisation of human cytomegalovirus nucleic acids and proteins in human colorectal cancer.

BACKGROUND: Colorectal cancer is the second most frequent cause of death from cancer in the USA, and most tumours arise sporadically with no clear cause or genetic predisposition. Human cytomegalovirus is a beta-herpesvirus that is endemic in the human population and can cause life-threatening disease in immunosuppressed adults. In vitro, human cytomegalovirus can transform cells and dysregulate many cellular pathways relevant to colon adenocarcinoma pathogenesis, especially those affecting the cell cycle, mutagenesis, apoptosis, angiogenesis, and cyclo-oxygenase-2 (COX-2) expression. We aimed to assess whether gene products of human cytomegalovirus could be detected in colorectal cancers. METHODS: We obtained formalin-fixed, paraffin-embedded pathological specimens of colorectal polyps, adenocarcinomas, and adjacent normal mucosa from 29 patients. To detect human cytomegalovirus proteins and nucleic acids, we used immunohistochemistry with two different monoclonal antibodies, in-situ hybridisation, and PCR with DNA sequencing. FINDINGS: Human cytomegalovirus proteins IE1-72 and pp65 were detected in a tumour cell-specific pattern in 14 (82%) of 17 and seven (78%) of nine colorectal polyps, respectively, and 12 (80%) of 15 and 11 (92%) of 12 adenocarcinomas, respectively, but not in adjacent non-neoplastic colon biopsy samples from the same patients (none of seven and none of two, respectively). Human cytomegalovirus infection of colon-cancer cells (Caco-2) in vitro resulted in specific induction of Bcl-2 and cyclo-oxygenase-2 proteins, both of which are thought to contribute to progression of colon cancer. INTERPRETATION: Human cytomegalovirus nucleic acids and proteins can be found that specifically localise to neoplastic cells in human colorectal polyps and adenocarcinomas, and virus infection can induce important oncogenic pathways in colon-cancer cells.