Keivan Shifteh

Diffusion-Tensor Imaging Implicates Prefrontal Axonal Injury in Executive Function Impairment Following Very Mild Traumatic Brain Injury

PURPOSE To determine whether frontal white matter diffusion abnormalities can help predict acute executive function impairment after mild traumatic brain injury (mTBI). MATERIALS AND METHODS This study had institutional review board approval, included written informed consent, and complied with HIPAA. Diffusion-tensor imaging and standardized neuropsychologic assessments were performed in 20 patients with mTBI within 2 weeks of injury and 20 matched control subjects. Fractional anisotropy (FA) and mean diffusivity (MD) images (imaging parameters: 3.0 T, 25 directions, b = 1000 sec/mm(2)) were compared by using whole-brain voxelwise analysis. Spearman correlation analyses were performed to evaluate associations between diffusion measures and executive function. RESULTS Multiple clusters of lower frontal white matter FA, including the dorsolateral prefrontal cortex (DLPFC), were present in patients (P < .005), with several clusters also demonstrating higher MD (P < .005). Patients performed worse on tests of executive function. Lower DLPFC FA was significantly correlated with worse executive function performance in patients (P < .05). CONCLUSION Impaired executive function following mTBI is associated with axonal injury involving the DLPFC.

Multifocal White Matter Ultrastructural Abnormalities in Mild Traumatic Brain Injury with Cognitive Disability: A Voxel-Wise Analysis of Diffusion Tensor Imaging

The purpose of the present study is to identify otherwise occult white matter abnormalities in patients suffering persistent cognitive impairment due to mild traumatic brain injury (TBI). The study had Institutional Review Board (IRB) approval, included informed consent and complied with the U.S. Health Insurance Portability and Accountability Act (HIPAA) of 1996. We retrospectively analyzed diffusion tensor MRI (DTI) of 17 patients (nine women, eight men; age range 26-70 years) who had cognitive impairment due to mild TBI that occurred 8 months to 3 years prior to imaging. Comparison was made to 10 healthy controls. Fractional anisotropy (FA) and mean diffusivity (MD) images derived from DTI (1.5 T; 25 directions; b = 1000) were compared using whole brain histogram and voxel-wise analyses. Histograms of white matter FA show an overall shift toward lower FA in patients. Areas of significantly decreased FA (p < 0.005) were found in the subject group in corpus callosum, subcortical white matter, and internal capsules bilaterally. Co-located elevation of mean diffusivity (MD) was found in the patients within each region. Similar, though less extensive, findings were demonstrated in each individual patient. Multiple foci of low white matter FA and high MD are present in cognitively impaired mild TBI patients, with a distribution that conforms to that of diffuse axonal injury. Evaluation of single subjects also reveals foci of low FA, suggesting that DTI may ultimately be useful for clinical evaluation of individual patients.

Diffusion tensor imaging abnormalities in patients with mild traumatic brain injury and neurocognitive impairment.

Objective: To determine if diffusion tensor imaging can differentiate patients with chronic cognitive impairment after mild traumatic brain injury (TBI) from normal controls. Methods: Ten patients with persistent cognitive impairment after mild TBI were evaluated at least 2 years after injury. Fractional anisotropy (FA) and apparent diffusion coefficient (ADC) were measured at white matter regions susceptible to axonal injury after TBI. Comparison was made to 10 normal controls. Results: Fractional anisotropy was significantly lower (4.5%; P = 0.01) and ADC higher (7.1%; P = 0.04) in patients at the left side of the genu of the corpus callosum. The mild TBI group also demonstrated a significant increase in FA within the posterior limb of the internal capsule bilaterally (left, 5.1%; P = 0.03; right, 1.9%; P = 0.04). Conclusions: These results demonstrate low FA and high ADC in the genu of the corpus callosum of mild TBI patients with persistent cognitive impairment, suggesting that permanent white matter ultrastructural damage occurs in mild TBI, and that such damage may be associated with persistent cognitive disability. Further longitudinal studies are warranted to elucidate the full importance of the findings.

Upper airway structure and body fat composition in obese children with obstructive sleep apnea syndrome.

RATIONALE Mechanisms leading to obstructive sleep apnea syndrome (OSAS) in obese children are not well understood. OBJECTIVES The aim of the study was to determine anatomical risk factors associated with OSAS in obese children as compared with obese control subjects without OSAS. METHODS Magnetic resonance imaging was used to determine the size of upper airway structure, and body fat composition. Paired analysis was used to compare between groups. Mixed effects regression models and conditional multiple logistic regression models were used to determine whether body mass index (BMI) Z-score was an effect modifier of each anatomic characteristic as it relates to OSAS. MEASUREMENTS AND MAIN RESULTS We studied 22 obese subjects with OSAS (12.5 ± 2.8 yr; BMI Z-score, 2.4 ± 0.4) and 22 obese control subjects (12.3 ± 2.9 yr; BMI Z-score, 2.3 ± 0.3). As compared with control subjects, subjects with OSAS had a smaller oropharynx (P < 0.05) and larger adenoid (P < 0.01), tonsils (P < 0.05), and retropharyngeal nodes (P < 0.05). The size of lymphoid tissues correlated with severity of OSAS whereas BMI Z-score did not have a modifier effect on these tissues. Subjects with OSAS demonstrated increased size of parapharyngeal fat pads (P < 0.05) and abdominal visceral fat (P < 0.05). The size of these tissues did not correlate with severity of OSAS and BMI Z-score did not have a modifier effect on these tissues. CONCLUSIONS Upper airway lymphoid hypertrophy is significant in obese children with OSAS. The lack of correlation of lymphoid tissue size with obesity suggests that this hypertrophy is caused by other mechanisms. Although the parapharyngeal fat pads and abdominal visceral fat are larger in obese children with OSAS we could not find a direct association with severity of OSAS or with obesity.

Adenotonsillectomy in Obese Children with Obstructive Sleep Apnea Syndrome: Magnetic Resonance Imaging Findings and Considerations

OBJECTIVE The reasons why adenotonsillectomy (AT) is less effective treating obese children with obstructive sleep apnea syndrome (OSAS) are not understood. Thus, the aim of the study was to evaluate how anatomical factors contributing to airway obstruction are affected by AT in these children. METHODS Twenty-seven obese children with OSAS (age 13.0 ± 2.3 y, body mass index Z-score 2.5 ± 0.3) underwent polysomnography and magnetic resonance imaging of the head during wakefulness before and after AT. Volumetric analysis of the upper airway and surrounding tissues was performed using commercial software (AMIRA®). RESULTS Patients were followed for 6.1 ± 3.6 mo after AT. AT improved mean obstructive apnea-hypopnea index (AHI) from 23.7 ± 21.4 to 5.6 ± 8.7 (P < 0.001). Resolution of OSAS was noted in 44% (12 of 27), but only in 22% (4 of 18) of those with severe OSAS (AHI > 10). AT increased the volume of the nasopharynx and oropharynx (2.9 ± 1.3 versus 4.4 ± 0.9 cm(3), P < 0.001, and 3.2 ± 1.2 versus 4.3 ± 2.0 cm(3), P < 0.01, respectively), reduced tonsils (11.3 ± 4.3 versus 1.3 ± 1.4 cm(3), P < 0.001), but had no effect on the adenoid, lingual tonsil, or retropharyngeal nodes. A small significant increase in the volume of the soft palate and tongue was also noted (7.3 ± 2.5 versus 8.0 ± 1.9 cm(3), P = 0.02, and 88.2 ± 18.3 versus 89.3 ± 24.4 cm(3), P = 0.005, respectively). CONCLUSIONS This is the first report to quantify volumetric changes in the upper airway in obese children with OSAS after adenotonsillectomy showing significant residual adenoid tissue and an increase in the volume of the tongue and soft palate. These findings could explain the low success rate of AT reported in obese children with OSAS and are important considerations for clinicians treating these children.

Novel retrospective, respiratory-gating method enables 3D, high resolution, dynamic imaging of the upper airway during tidal breathing.

A retrospective, respiratory‐gated technique for measuring dynamic changes in the upper airway over the respiratory cycle was developed, with the ultimate goal of constructing anatomically and functionally accurate upper airway models in obstructive sleep apnea patients.

Rhino‐sinus involvement in children with obstructive sleep apnea syndrome

Obstructive sleep apnea syndrome (OSAS) is commonly associated with adenotonsillar hypertrophy. We hypothesized that respiratory perturbations extend to other regions of the upper respiratory tract in such children, particularly to rhino‐sinus regions.

CT-guided radiofrequency ablation in the palliative treatment of recurrent advanced head and neck malignancies.

PURPOSE To evaluate the safety and effectiveness of computed tomography (CT)-guided radiofrequency (RF) ablation in the palliative treatment of recurrent advanced head and neck cancers. MATERIALS AND METHODS From November 2002 to January 2005, the authors identified 14 patients (median age, 61 years) with 14 recurrent advanced primary head and neck malignancies who underwent 27 CT-guided RF ablation applications during 20 sessions at their institution. RF ablation was performed in all patients with the intent of palliative therapy. Radiologic tumor response was assessed by using Response Evaluation Criteria in Solid Tumors. Patients were assessed clinically by means of University of Washington Head and Neck Quality of Life questionnaires. RESULTS Technical success in tumor targeting and electrode deployment was 100%. University of Washington quality of life surveys completed by six of 14 patients (43%) showed an index increase by a median of 3.1 percentage points, with four of six patients (67%) demonstrating improvement. Three major complications (in 27 applications, 11%) occurred 7 days to 2 weeks after the procedure. These included stroke, carotid blowout leading to death, and threatened carotid blowout with subsequent stroke. Retrospective analysis of intraprocedural CT scans revealed that the retractable electrodes were within 1 cm of the carotid artery during ablation in these cases. CONCLUSIONS RF ablation in patients with advanced head and neck malignancies is feasible and effective for palliation. CT-guidance provides accurate probe placement and electrode deployment. The energy level used and proximity of the ablation sphere to the carotid artery may predispose to vascular complications.

Radiofrequency Ablation of Advanced Head and Neck Cancer

OBJECTIVE To determine if the application of radiofrequency ablation to advanced head and neck cancer (HNC) would result in local control of the tumor. DESIGN Radiofrequency ablation was applied to advanced head and neck malignant tumors in the participants of this nonrandomized controlled trial. SETTING Academic tertiary care medical center. PARTICIPANTS Twenty-one participants with recurrent and/or unresectable HNC who failed treatment with surgery, radiation, and/or chemotherapy were selected for the trial. Patients deemed appropriate for curative standard radiation or surgery were not accepted as participants. INTERVENTION Radiofrequency ablation was applied to head and neck tumors under general anesthesia and computed tomographic scan guidance. MAIN OUTCOME MEASURES The primary end point was local control. Computed tomographic scan tumor measurements were used to assess response by standard response evaluation criteria in solid tumors (RECIST) guidelines. Secondary outcome measures included survival and quality of life. RESULTS Eight of 13 participants had stable disease after intervention. Median survival was 127 days, and an improvement in University of Washington quality-of-life scores was noted. Adverse outcomes included 1 death due to carotid hemorrhage and 2 strokes. CONCLUSION Radiofrequency ablation is a palliative treatment alternative that shows promise in addressing the challenges of local control and quality of life in patients with incurable HNC who have failed standard curative treatment.

Metastatic Apocrine Carcinoma of the Scalp: Prolonged Response to Systemic Chemotherapy

A 20-year-old African American man presented with alopecia and a firm, nontender nodule over the left forehead with keloid appearance that had been increasing in size over several weeks. The resection specimen revealed poorly differentiated apocrine carcinoma. Sixteen months later, he developed a frontal scalp mass (Fig 1A) with left postauricular lymph node and left parotid enlargement (Fig 1B); histopathology confirmed recurrence of apocrine carcinoma, situated entirely in the superficial and deep dermis (Fig 2A). This lesion demonstrated both squamous (Fig 2B, white arrows) and apocrine differentiation (Fig 2B, black arrows; higher power view in Fig 2C), and lymphatic tumor emboli were present (Fig 2D). A chest computed tomography scan noted multiple lung metastases (Fig 3A) and a lytic lesion of the right clavicular head. In addition to a painful right clavicle, the patient reported pain and swelling of his left ankle, and an x-ray was consistent with hypertrophic osteoarthropathy of the tibia and fibula. Zoledronic acid was administered, and his bone pain resolved. The patient received palliative radiotherapy to the clavicular lesion, followed by chemotherapy cycles of paclitaxel (200 mg/m) and carboplatin (area under the curve, 6) every 21 days. Follow-up imaging showed a remarkable response to chemotherapy (Fig 3B), which was durable for 16 months. The patient ultimately died from unresectable and refractory scalp recurrence with brain invasion nearly 55 months after initial diagnosis. Apocrine (sweat gland) malignancies are rare, with only scattered case reports in the literature, and carry high potential of lymphatic and vascular spread leading to lung, liver, and bone metastasis. The axilla and the anogenital skin are the most common sites of primary disease, although apocrine carcinomas of the eyelid, scalp, ear, chest, lip, foot, toe, and finger have been reported. Clinically, the disease manifests as nontender, single, or multiple firm superficial masses with red to purple discoloration. Histologically, tumor size, degree of differentiation, and resection margins have important prognostic value. Although it is uncertain whether differentiation between eccrine and apocrine sweat gland carcinoma is of any clinical utility, they are sometimes reported separately in the literature. Microscopically, both have the appearance of adenocarcinoma, with periodic acid–Schiff (PAS) -positive cells because of the presence of glycogen granules. However, after diastase digestion, apocrine tumor cells retain the PAS stain and are therefore diastase resistant, while eccrine tumor cells are diastase sensitive. Local treatment of sweat gland carcinoma consists of wide local excision and skin grafting; as with other skin malignancies, a surgical margin of 1 to 2 cm would be considered adequate. Mohs micrographic surgery has also been used in functionally or cosmetically limiting locations without compromising the oncologic outcome in the cases of small, well-differentiated tumors. In moderate to poorly differentiated tumors, lymph node involvement has been reported in approximately 50% of cases. However, prophylactic lymph node resection does not appear to improve survival or decrease recurrence rates. The use of adjuvant radiotherapy to prevent local recurrence is not wellestablished. One report suggested radiosensitivity of these tumors, and adjuvant radiation was therefore recommended in high-risk cases (ie, unusually large tumors 5 cm , positive surgical margins 1 cm , and moderate to poorly differentiated tumors