CEDNIK syndrome results from loss-of-function mutations in SNAP29.

BACKGROUND: CEDNIK (cerebral dysgenesis, neuropathy, ichthyosis and keratoderma) syndrome is a rare genodermatosis which was shown 5 years ago in one family to be associated with a loss-of-function mutation in SNAP29, encoding a member of the SNARE family of proteins. Decrease in SNAP29 expression was found to result in abnormal lamellar granule maturation leading to aberrant epidermal differentiation and ichthyosis. OBJECTIVES: To delineate the molecular consequences of disease-causing mutations in SNAP29. METHODS: We used direct sequencing, in vitro mutagenesis and three-dimensional organotypic cell cultures. RESULTS: We identified a novel homozygous insertion in SNAP29 (c.486insA) in two sibs presenting with ichthyosis and dysgenesis of the corpus callosum. In vitro transfection experiments indicated that this mutation results in SNAP29 loss-of-function. Further substantiating this notion, we could replicate histological features typical for CEDNIK syndrome in three-dimensional primary human keratinocyte organotypic cell cultures downregulated for SNAP29. CONCLUSIONS: The identification of a second mutation in SNAP29 in the present study definitely establishes a causal relationship between defective function of SNAP29 and the pleiotropic manifestations of CEDNIK syndrome. Our present and previous data position SNAP29 as an essential component of the epidermal differentiation machinery.

Morphological study of the spinal canal content for subarachnoid endoscopy.

STUDY DESIGN AND OBJECTIVE: This study was designed to examine the morphology of the spinal dural sac and contents, using magnetic resonance imaging in order to define the inner geometrical dimensions that confine the manoeuvre of an endoscope inserted in the lumbar region and along the thoracic and cervical spine. BACKGROUND: The morphology of the spine has been studied since the development of myelography. However, most studies have measured the diameters of the spinal cord only, not the size of the subarachnoid space. In addition, the few studies available on the subarachnoid space have focused on the cervical spine, leaving a near-complete dearth of data on the subarachnoid space dimensions along the thoracic spine. METHODS: Based on MRI images of the spine from 42 patients, the dimensions of the spinal cord, dural sac, and subarachnoid space were measured at mid-vertebral and inter-vertebral disc levels. RESULTS: It was found that at each selected transverse level, the subarachnoid space tends to be symmetrical on the right and left sides of the cord, and measures 2.5 mm on average. However, the posterior and anterior segments, measured on the mid-sagittal plane, are generally asymmetrical and vary widely in size, ranging from 1 to 5 mm. These measurements match those found in previous studies, where these are available. The coefficient of variance for the dimensions of the subarachnoid space is as high as 42.4%, while that for the dimensions of the spinal cord is 10-15%. CONCLUSIONS: The findings presented here expand our knowledge of the spinal canal's morphology, and show that an endoscope designed to travel within the subarachnoid space must be smaller than 2.5 mm in diameter.

Impaired "affective theory of mind" is associated with right ventromedial prefrontal damage.

OBJECTIVE: To examine the hypothesis that patients with ventromedial (VM) frontal lesions are impaired in the affective rather than cognitive facets of theory of mind (ToM). BACKGROUND: Prefrontal brain damage may result in impaired social behavior, especially when the damage involves the orbitofrontal/VM prefrontal cortex (PFC). It has been previously suggested that deficits in ToM may account for such aberrant behavior. However, inconsistent results have been reported, and different regions within the frontal cortex have been associated with ToM impairment. METHOD: The performance of 26 patients with localized lesions in the PFC was compared with responses of 13 patients with posterior lesions and 13 normal control subjects. Three ToM tasks differing in the level of emotional processing involved were used: second-order false belief task, understanding ironic utterances, and identifying social faux pas. RESULTS AND CONCLUSIONS: The results indicated that patients with VM (but not dorsolateral) prefrontal lesions were significantly impaired in irony and faux pas but not in second-order false belief as compared with patients with posterior lesions and normal control subjects. Lesions in the right VM area were associated with the most severe ToM deficit. These results are discussed in terms of the cognitive and affective facets of "mind-reading" processes mediated by the VM cortex.

Impairment in cognitive and affective empathy in patients with brain lesions: anatomical and cognitive correlates.

The present study was designed to examine the degree of impairment in cognitive and affective empathy among patients with focal brain lesions, and the contribution of specific cognitive abilities (such as cognitive flexibility and processing of emotional information), to empathy. The cognitive and affective empathic response of patients with localized prefrontal lesions (n=36) was compared to responses of patients with parietal lesions (n=15) and healthy control subjects (n=19). Results indicate that patients with prefrontal lesions (especially those with lesions involving the orbitoprefrontal and medial regions) were significantly impaired in both cognitive and affective empathy as compared to parietal patients and healthy controls. When the damage was restricted to the prefrontal cortex, either left- or right-hemisphere lesions resulted in impaired empathy. However, when the lesion involved the right hemisphere, patients with parietal lesions were also impaired. The pattern of relationships between cognitive performance and empathy suggested dissociation between the cognitive correlates of affective and cognitive empathy.

Hyperbaric oxygen therapy as a treatment for stage-I avascular necrosis of the femoral head.

Avascular necrosis (AVN) of the head of the femur is a potentially crippling disease which mainly affects young adults. Although treatment by exposure to hyperbaric oxygen (HBO) is reported as being beneficial, there has been no study of its use in treated compared with untreated patients. We selected 12 patients who suffered from Steinberg stage-I AVN of the head of the femur (four bilateral) whose lesions were 4 mm or more thick and/or 12.5 mm or more long on MRI. Daily HBO therapy was given for 100 days to each patient. All smaller stage-I lesions and more advanced stages of AVN were excluded. These size criteria were chosen in order to compare outcomes with an identical size of lesion in an untreated group described earlier. Overall, 81% of patients who received HBO therapy showed a return to normal on MRI as compared with 17% in the untreated group. We therefore conclude that hyperbaric oxygen is effective in the treatment of stage-I AVN of the head of the femur.

CT angiography of the carotid arteries in trauma to the neck.

OBJECTIVES: serious vascular injuries to the neck may be asymptomatic or masked by other life-threatening conditions. Angiography, the "gold standard" vascular imaging modality, is an invasive procedure. Moreover, it is time-consuming and thus may delay a needed vascular intervention. The results of screening angiography are negative in more than 80% of cases. Therefore other less invasive and faster screening tests, such as the Doppler ultrasound and magnetic resonance angiography, have been tested. This retrospective study was done to evaluate the use of CT angiography (CTA) in suspected vascular injuries of the neck. METHODS: from 1995 to 1998, 16 patients with suspected traumatic carotid artery injury underwent CTA. Twelve of these patients had penetrating injuries and four had blunt injuries to the neck. CTAs were obtained by Elscint Twin Flash Spiral Scanner, while MIP reconstructions were carried out on an Omnipro, Elscint (Indy, Silicon Graphics) work station and interpreted by a radiologist. RESULTS: all the CTAs were diagnostic. Positive findings included one complete tear of the right common carotid artery (confirmed by surgery) due to a penetrating injury and one bilateral internal carotid artery thrombosis after blunt injury to the neck. In addition, three patients with multiple trauma were operated on, due to either proximity only or questionable neurological findings. Surgical exploration confirmed the negative findings seen on CTA. CONCLUSION: CT angiography of the carotid arteries in cervical trauma may be used as an accurate decisive tool for a needed surgical intervention. More studies with larger number of patients and comparison with angiography are needed.

Color-coded duplex ultrasound compared to CT angiography for detection and quantification of carotid artery stenosis.

OBJECTIVE: The purpose of this study was to compare findings on color-coded duplex ultrasound and CT angiography for grading internal carotid artery stenosis, and to investigate whether both these imaging modalities are necessary for an accurate diagnosis of carotid stenosis in the pre-surgical assessment of the internal carotid artery. PATIENTS AND METHODS: We examined 92 internal carotid arteries from 46 randomly chosen patients with suspected carotid stenosis by color-coded duplex ultrasound and by three-dimensional CT angiography (CTA). This retrospective study adhered to international guidelines with gradings of mild, moderate, severe, and occlusive carotid disease. RESULTS: The study demonstrated agreement between the degree of stenosis found on color-coded duplex ultrasound and that found on CTA in 78% of cases overall and in 79% of patients requiring surgical intervention. When compared to CTA, color-coded duplex ultrasound yielded a sensitivity of 78.9% and a specificity of 96.3%. Although findings on color-coded duplex ultrasound and CTA were comparable, disagreement affecting treatment decision occurred in 10:92 arteries. CONCLUSION: CTA was not found to be beneficial for patients exhibiting mild stenosis on color-coded duplex ultrasound, as none of the mild groupings found by sonography were interpreted as severe or occluded by CTA. However, CTA may be an important adjunct to color-coded duplex ultrasound regarding the categories of moderate, severe and occluded when carotid endarterectomy is considered.

Hypoplasia of the inferior vena cava with azygous continuation presenting as recurrent leg deep vein thrombosis.

Azygous continuation of the inferior vena cava is a rare congenital malformation. It occurs because of atresia of the retrohepatic segment of the inferior vena cava. The disorder has been described mainly as an incidental finding associated with a number of congenital malformations, including cardiovascular, tracheobronchial, and other visceral malformations. Therapeutic intervention is aimed primarily at accompanying malformations. We report a case of hypoplasia of the inferior vena cava with azygous continuation in a 30-year-old man who presented with recurrent deep venous thrombosis.

Posterior cortical atrophy variants of Alzheimer's disease.

Posterior cortical atrophy (PCA) was first described by Benson in 1988 and, since then, has been regarded as a variant of Alzheimer's disease. We present 2 patients with symptoms suggestive of PCA and 2 patients with apraxia as the initial manifestation. Primary motor and sensory modalities were intact. Mild memory impairment was present early in the course of the disease and gradually worsened. Parieto-occipital atrophy was evident on brain MRI. HMPAO-SPECT demonstrated parieto-occipital hypoperfusion significantly different from the temporoparietal hypoperfusion usually described in senile dementia of the Alzheimer type. These findings suggest that HMPAO-SPECT can help in diagnosing atypical variants of Alzheimer's disease. We suggest that PCA represents two clinically related behavioral phenotypes: PCA with predominantly apraxia manifestations and PCA with predominantly visuospatial disturbances. Copyrightz1999S.KargerAG,Basel

Carboplatin and etoposide for recurrent malignant glioma following surgical and radiotherapy failure: A clinical study conducted at the Northern Israel Oncology Center.

BACKGROUND AND OBJECTIVES: We conducted a phase II study using carboplatin and etoposide on patients with recurrent malignant glioma to investigate tumor response. METHODS: From January 1995 to March 1997, 21 patients with recurrent malignant glioma were treated with a carboplatin (300 mg/m(2), day 1)/etoposide (100 mg/m(2), days 1-3) regimen every 3-4 weeks. The following radiologic parameters were evaluated: tumor size, central lucency, degree of contrast enhancement, and mass effect. No patient had received chemotherapy previously. Dose escalation corresponded to hematologic tolerance and to general and neurologic performance status. Most patients were treated postoperatively with involved field radiotherapy followed by a boost to the tumor area, as defined on the presurgery computed tomography scan or on magnetic resonance imaging. Mean interval to introduction of chemotherapy was 8.8 months (range, 7-36 months). Patients received a mean of four cycles [range, 2-8 cycles]. RESULTS: Only 2 patients showed moderate radiological response, while 12 patients died of progressive disease. Mean time to progression following discontinuation of chemotherapy was 5.8 months (range, 1-11 months). The other patients survived with persistent disease and are being treated palliatively. Toxicity was manageable (1, neutropenic sepsis; 1, thrombocytopenia (45,000/mm(3)); 2, temporarily elevated transaminase level; 2, steroid-induced erosive gastritis). CONCLUSIONS: This phase II regimen proved to be ineffective in recurrent malignant glioma. Further studies incorporating innovative drug regimens and schedules are warranted. J. Surg. Oncol., 1999;71:167-170.

Clinical and radiographic response in three children with recurrent malignant cerebral tumors with high-dose tamoxifen.

The purpose of this study was to deliver tamoxifen as antiangiogenic therapy to children with recurrent progressive malignant brain tumors. Tamoxifen was administered orally in very high dosage to one child as monotherapy and to two children in combination with oral etoposide and dexamethasone. One boy was diagnosed with high-grade astrocytoma in the brain stem, one girl with anaplastic ependymoma of the fourth ventricule, and one girl with high-grade astrocytoma in the midbrain. Conventional treatment with multiple surgeries, first- and second-line chemotherapy, and external beam therapy had failed. Tumor reduction was seen in radiographic images together with clinical improvement in 2 children, and clinical and radiographic halting of tumor progression was demonstrated in the patient with anaplastic ependymoma. None of the patients developed complications from the treatment. Follow up of the patients ranged from 15 to 30 months with a mean of 17 months. These encouraging preliminary results suggest a potential for this type of therapy. More studies are needed to start clinical trials and prove that angiostatic activity may contribute to the therapeutic effect of antiestrogens in estrogen receptor-negative tumors.

[Temporal hemianopia and diabetes insipidus following head injury].

Bitemporal hemianopia and diabetes insipidus following head injury are caused by a lesion in the center of the optic chiasm, together with injury to the adjacent pituitary stalk or the hypothalamus. This combination was thought to be a rare complication of severe head injury. The case of a 16-year-old male is presented, which together with recent reports suggests that this relatively under-recognized syndrome is not infrequent, that it may follow even minor head injury, and that magnetic resonance imaging can demonstrate the chiasmal lesion.

Melatonin replacement corrects sleep disturbances in a child with pineal tumor.

A child with a germ cell tumor involving the pineal region had marked suppression of melatonin secretion associated with severe insomnia. Exogenous melatonin (3 mg in the evening) for 2 weeks restored sleep continuity, as demonstrated by objective monitoring of rest-activity cycles. This case report provides direct evidence of the essential role of melatonin in normal sleep.

Recurrent retinal artery obstruction as a presenting symptom of ophthalmic artery aneurysm: a case report.

BACKGROUND: Retinal artery obstruction is an ophthalmic emergency requiring immediate treatment. Recurrent episodes are the result of thromboembolic seeding and necessitate diagnostic efforts to find a possible source for this seeding. The most common sources of such seeding are the valves of the heart and the carotid arteries. CASE REPORT: We describe a case of a 25-year-old man who had recurrent episodes of retinal artery obstruction due to embolic spread. DISCUSSION: We suggest the origin of the embolic spread to be a post-traumatic ophthalmic artery aneurysm. The immediate and long-term treatment given to the patient are described, the present case is compared to earlier reports, and the unusual clinical picture and suggested treatment are discussed.

Radiation-induced primary brain lymphoma: a case report.

A patient who developed primary brain lymphoma 6 years following whole brain irradiation due to a low-grade glioma is described. The patient had no evidence of congenital or acquired immunodeficiency state and achieved a good and prompt response to aggressive chemotherapy, including high-dose methotrexate. The previous radiation therapy is implicated in the etiology of the lymphoma because of the geometric coincidence, the relatively long latency period and the different histology. A brief review of current literature is reported.