Loss of function of PCDH12 underlies recessive microcephaly mimicking intrauterine infection.

OBJECTIVE: To identify the genetic basis of a recessive syndrome characterized by prenatal hyperechogenic brain foci, congenital microcephaly, hypothalamic midbrain dysplasia, epilepsy, and profound global developmental disability. METHODS: Identification of the responsible gene by whole exome sequencing and homozygosity mapping. RESULTS: Ten patients from 4 consanguineous Palestinian families manifested in utero with hyperechogenic brain foci, microcephaly, and intrauterine growth retardation. Postnatally, patients had progressive severe microcephaly, neonatal seizures, and virtually no developmental milestones. Brain imaging revealed dysplastic elongated masses in the midbrain-hypothalamus-optic tract area. Whole exome sequencing of one affected child revealed only PCDH12 c.2515C>T, p.R839X, to be homozygous in the proband and to cosegregate with the condition in her family. The allele frequency of PCDH12 p.R839X is <0.00001 worldwide. Genotyping PCDH12 p.R839X in 3 other families with affected children yielded perfect cosegregation with the phenotype (probability by chance is 2.0 × 10(-12)). Homozygosity mapping revealed that PCDH12 p.R839X lies in the largest homozygous region (11.7 MB) shared by all affected patients. The mutation reduces transcript expression by 84% (p < 2.4 × 10(-13)). PCDH12 is a vascular endothelial protocadherin that promotes cellular adhesion. Endothelial adhesion disruptions due to mutations in OCLN or JAM3 also cause congenital microcephaly, intracranial calcifications, and profound psychomotor disability. CONCLUSIONS: Loss of function of PCDH12 leads to recessive congenital microcephaly with profound developmental disability. The phenotype resembles Aicardi-Goutières syndrome and in utero infections. In cases with similar manifestations but no evidence of infection, our results suggest consideration of an additional, albeit rare, cause of congenital microcephaly.

4D MRI for the Localization of Parathyroid Adenoma: A Novel Method in Evolution.

The sestamibi scan (MIBI) and ultrasound (US) are used for preoperative localization of parathyroid adenoma (PTA), with sensitivity as high as 90%. We developed 4-dimensional magnetic resonance imaging (4D MRI) as a novel tool for identifying PTAs. Eleven patients with PTA were enrolled. 4D MRI from the mandible to the aortic arch was used. Optimization of the timing of image acquisition was obtained by changing dynamic and static sequences. PTAs were identified in all except 1 patient. In 9 patients, there was a complete match between the 4D MRI and the US and MIBI, as well as with the operative finding. In 1 patient, the adenoma was correctly localized by 4D MRI, in contrast to the US and MIBI scan. The sensitivity of the 4D MRI was 90% and after optimization, 100%. Specificity was 100%. We concluded that 4D MRI is a reliable technique for identification of PTAs, although more studies are needed.

A Novel Radiographic Sign and a New Classifying System in Mastoiditis-Related Epidural Abscess.

OBJECTIVE: To describe a novel radiographic sign ("halo") and a new classification method of an evolving perisigmoid epidural abscess and present its correlation with intraoperative findings. STUDY DESIGN: Retrospective and prospective cohort study in a tertiary academic children's hospital. METHODS: The retrospective arm (15 children) was conducted between 1998 and 2007 and the prospective arm (11 children) between 2008 and 2013. The computerized tomographic appearance of the perisigmoid region was classified into four groups: Class I, normal; Class II, smooth halo; Class III, nodular halo 4 mm or less in diameter; and Class IV, gross nodular halo more than 4 mm in diameter. Intraoperative findings of the perisigmoid region were compared with the preoperative scan results. RESULTS: The correlation between preoperative imaging and intraoperative findings of the retrospective arm was highly significant (p = 0.007). The correlation between the preoperative imaging studies and intraoperative findings of the prospective arm was also highly significant (p = 0.005). The interobserver agreement for the proposed classification method was high (Cohen kappa score, 0.76; weighted kappa score, 0.84). CONCLUSION: A novel radiographic sign ("halo") and a new classification method for an evolving perisigmoid epidural abscess in acute mastoiditis are described. A thin and smooth halo sign is not indicative of a true abscess formation. Gross perisigmoid granular changes, however, are highly suggestive of an epidural abscess that warrants surgical intervention.

[Anterior clinoid process mucocele causing optic nerve compression].

A mucocele is a collection of mucus lined by mucus-secreting epithelium of a paranasal sinus. The anterior clinoid process may become pneumatized during the development of the skull base. Rarely, an anterior clinoid process mucocele may form in this air space. We report a patient with anterior clinoid process mucocele who presented with visual loss and limited motility in the affected eye, and underwent surgery to decompress the orbital apex and optic nerve. We also review the literature regarding this rare diagnosis.

Antral computerized tomography pre-operative evaluation: relationship between mucosal thickening and maxillary sinus function.

OBJECTIVES: to assess the correlation between maxillary sinus inferior mucosal thickening and sinus outflow obstruction. MATERIAL AND METHODS: the study included 280 computerized tomography (CT) scans (560 maxillary sinuses). CT aimed to assess sinusitis; trauma to the face and intubated patients were excluded. Mucosal thickening was graded as < 5 mm (1), < 10 mm (2), < 15 mm (3), < 20 mm (4) and > 20 mm (5), and classified by appearance as normal, rounded, circumferential, irregular, or complete. Maxillary sinus outflow was classified as patent or obstructed. RESULTS: mucosal thickening was found in 36.1% of the maxillary sinuses, graded as 31.2% (1), 34.2% (2), 12.9% (3), 5.4% (4) and 16.3% (5), and classified as rounded (11.8%), irregular (10.4%), circumferential (8.8%) and complete (5.2%). Sinus outflow was obstructed in 15% of the scans. Mucosal thickening of < 5 mm (11.1%), < 10 mm (36.2%) and > 10 mm (74.3%) was associated with sinus obstruction (P<0.0001). Rounded (6.1%), circumferential (55.2%), irregular (38.8%) and complete (100%) mucosal appearances were associated with sinus obstruction (P<0.001). When statistically combined, a substantial risk for sinus obstruction was observed with irregular mucosal appearance of > 5 mm (56.5% for grade 2 up to 82.6% for grades 3-5) and circumferential appearance (21.4% for grade 1 up to 100% for grades 3-5). A low risk for obstruction was found with the rounded appearance (mean 6.1%). CONCLUSIONS: irregular (> 5 mm), circumferential and complete mucosal appearance are associated with an increased risk for sinus outflow obstruction and an ENT consultation is recommended. A rounded mucosal appearance of any grade is associated with a low risk for sinus obstruction. Routine CT scans, including the maxillary sinus ostium, are recommended.

Selective impairment of prediction error signaling in human dorsolateral but not ventral striatum in Parkinson's disease patients: evidence from a model-based fMRI study.

Animal studies have found that the phasic activity of dopamine neurons during reward-related learning resembles a "prediction error" (PE) signal derived from a class of computational models called reinforcement learning (RL). An apparently similar signal can be measured using fMRI in the human striatum, a primary dopaminergic target. However, the fMRI signal does not measure dopamine per se, and therefore further evidence is needed to determine if these signals are related to each other. Parkinson's disease (PD) involves the neurodegeneration of the dopamine system and is accompanied by deficits in reward-related decision-making tasks. In the current study we used a computational RL model to assess striatal error signals in PD patients performing an RL task during fMRI scanning. Results show that error signals were preserved in ventral striatum of PD patients, but impaired in dorsolateral striatum, relative to healthy controls, a pattern reflecting the known selective anatomical degeneration of dopamine nuclei in PD. These findings support the notion that PE signals measured in the human striatum by the BOLD signal may reflect phasic DA activity. These results also provide evidence for a deficiency in PE signaling in the dorsolateral striatum of PD patients that may offer an explanation for their deficits observed in other reward learning tasks.

Aggressive intracranial dural arteriovenous fistula presenting with cerebrospinal fluid rhinorrhea: case report.

OBJECTIVE: This is the first report of an aggressive dural arteriovenous fistula presenting with rhinorrhea. It demonstrates the importance of recognizing increased intracranial pressure, and its underlying cause, as the predisposing factor to a spontaneous cerebrospinal fluid leak because this carries implications for management. CLINICAL PRESENTATION: Ten years after minor trauma and directly after an intercontinental flight, a 43-year-old woman presented with rhinorrhea. Right-sided pulsatile tinnitus had been present for the past 9 years. Imaging demonstrated an intracranial dural arteriovenous fistula of the right transverse sinus with cortical venous reflux. Magnetic resonance imaging findings indicated long-standing increased intracranial pressure. INTERVENTION: The fistula was treated by endovascular means, using both transvenous and transarterial approaches, which led to immediate relief of the tinnitus and resolution of the rhinorrhea within 4 days. CONCLUSION: A dural arteriovenous fistula should be included in the differential diagnosis of underlying causes of increased intracranial pressure when examining a patient with a cerebrospinal fluid leak. Treatment of the fistula should precede attempts to treat the rhinorrhea, especially if the fistula has cortical venous reflux.

Acute esotropia after epidural anesthesia.

BACKGROUND: Cranial nerve palsy after dural puncture is an uncommon complication. The sixth cranial nerve is the most commonly affected because of its long intracranial course. We report a case of acute comitant esotropia that occurred after unintentional dural puncture. CASE: A young woman presented with acute onset comitant esotropia 1 week after epidural anesthesia for a normal vaginal delivery during which the dura was unintentionally punctured. Magnetic resonance imaging revealed diffuse pachymeningeal enhancement, typically seen after dural puncture. Resolution was spontaneous. CONCLUSION: Puncture of the dura should be considered when acute strabismus is diagnosed shortly after epidural anesthesia.

Attachment-oriented endoscopic surgical strategy for sinonasal inverted papilloma.

BACKGROUND: It is well documented that inverted papillomas (IP) have a localized attachment site. Still, instead of concentrating on the attachment site, endoscopic surgeons often perform an extended resection similar to the one achieved after external surgery. OBJECTIVE: Our objective was to evaluate an attachment-oriented endoscopic surgical strategy and to determine IP attachment diameter and location. METHODS: A prospective study was conducted. Thirty-three consecutive patients who underwent endoscopic IP excision (2001--2007) were enrolled. Thirty patients had adequate follow-up. Attachment diameters were measured in 25/33 patients. Surgery included debulking, identifying the precise mucosal attachment site, subperiosteal dissection and excision of the attachment, frozen section control, and resection/drilling of underlying bone. RESULTS: The mean measured attachment diameter (n = 25) was 8.4 +/- 6 mm (range, 3-23 mm). Attachment locations included maxillary sinus (39%), ethmoid sinus (21%), nasal cavity (21%), frontal sinus (6%), sphenoid sinus (6%), lamina papyracea (3%), and cribriform plate (3%). The mean follow-up (n = 30) was 40 +/- 21 months. Three patients had Krouse stage 1, 10 patients had stage 2, and 17 patients had stage 3. Nine patients had undergone previous surgeries. After attachment-oriented endoscopic surgery, three patients had persistent disease. Nasolacrimal duct stenosis was the only complication (n = 1). CONCLUSION: Even advanced IP have small attachments. Their Identification facilitates efficacious resection with minimal morbidity.

The role of the otorhinolaryngologist in the management of central skull base osteomyelitis.

BACKGROUND: Skull base osteomyelitis (SBO) typically evolves as a complication of external otitis in diabetic patients and involves the temporal bone. Central SBO (CSBO) mainly involves the sphenoid or occipital bones without coexisting external otitis. We characterized a group of patients with CSBO. The endoscopic nasopharyngeal and clival biopsy technique is described. METHODS: Medical records of patients diagnosed as having SBO were retrospectively analyzed (from 2001 to 2006). Patients' symptoms and signs, laboratory findings, imaging characteristics, endoscopic clival and periclival histopathology results, treatment, and outcome were retrieved. RESULTS: Of 20 patients with SBO, 6 patients without external otitis were studied (age range, 54-76 years; 5 men; mean follow-up, 21 months). All patients suffered from unilateral headache, three of six patients had serous otitis media (SOM), three of six patients had cranial nerve (CN) palsies, and five of six patients had elevated acute-phase reactants. Computed tomography (CT) findings were clival cortical bone erosion and adjacent soft tissue swelling. Magnetic resonance (MR) findings were texture changes and enhancement of the involved bones and soft tissues. Biopsy specimens revealed chronic inflammation. All six patients were treated with antibiotics for 3-6 months. Headache disappeared in five of six patients, SOM resolved in two of three patients, and CN palsies partially recovered in two of three patients. Imaging findings improved in five of six patients. CONCLUSION: CSBO may mimic malignancy and represents a diagnostic challenge. Typical clinical picture and imaging findings together with a positive response to ciprofloxacin may suffice to establish the diagnosis and obviate the need for biopsies. When in doubt, nasopharyngeal and clival biopsies are performed to rule out malignancy.

Sonographic features of senile scleral calcification.

BACKGROUND AND OBJECTIVE: To describe the sonographic features of senile scleral calcification using ultrasound biomicroscopy. PATIENTS AND METHODS: Four patients in whom senile scleral calcifications were found incidentally on computed tomography studies underwent ultrasound biomicroscopy examination. RESULTS: The senile scleral calcification was bilateral in three patients and unilateral in one patient. In all patients, the calcified material created the anterior shadowing typical of calcified lesions. The ultrasound biomicroscopy study localized the senile scleral calcification to the subconjunctival layer, superficially above the sclera, and anterior to the horizontal muscles. CONCLUSIONS: This is the first description of the ultrasound biomicroscopy features of senile scleral calcification. Ultrasound biomicroscopy may serve as a good tool for the accurate localization of the plaque.

Systemic corticosteroids for allergic fungal rhinosinusitis and chronic rhinosinusitis with nasal polyposis: a comparative study.

OBJECTIVES: To compare the effect of preoperative high-dose systemic corticosteroids on the radiographic and endoscopic appearance of allergic fungal rhinosinusitis (AFRS) and chronic rhinosinusitis with nasal polyposis (CRSwNP). STUDY DESIGN AND SETTING: Eight AFRS and 10 CRSwNP patients underwent computed tomographic (CT) scans and then received preoperative 1 mg/kg prednisone for 10 days. CT scans were repeated 1 day before surgery and compared with pretreatment scans (Lund-MacKay radiologic scoring system). The endoscopic appearance was recorded intraoperatively. RESULTS: The score dropped from 16 (66.4%) to 4.75 in the AFRS group and from 18.4 (23%) to 14.1 in the CRSwNP group (P=0.0064). Intraoperatively, most sinus mucosal surfaces appeared normal in the AFRS patients but were markedly edematous in the CRSwNP patients. CONCLUSION: Radiographic response of AFRS to systemic corticosteroids is significantly greater compared with CRSwNP. This finding is supported by endoscopic observation.

Stafne bone cavity--magnetic resonance imaging.

A case of Stafne bone cavity (SBC) affecting the body of the mandible of a 51-year-old female is reported. The imaging modalities included panoramic radiograph, computed tomography (CT) and magnetic resonance (MR) imaging. Panoramic radiograph and CT were able to determine the outline of the cavity and its three dimensional shape, but failed to precisely diagnose the soft tissue content of the cavity. MR imaging demonstrated that the bony cavity is filled with soft tissue that is continuous and identical in signal with that of the submandibular salivary gland. Based on the MR imaging a diagnosis of SBC was made and no further studies or surgical treatment were initiated. MR imaging should be considered the diagnostic technique in cases where SBC is suspected. Recognition of the lesion should preclude any further treatment or surgical exploration.

Palpitations: could they be neurogenic? A case report.

BACKGROUND: Palpitations usually occur in patients with arrhythmias of cardiac origion, in conditions associated with increased catecholamine levels, and in psychiatric disorders. A rare etiology of palpitations is seizures with autonomic features. REVIEW SUMMARY: We report a 24-year-old man with a several-week history of episodic palpitations, weakness, dizziness, and presyncopal phenomena. Subsequent events included loss of consciousness, with postevent confusion and tonic movements. A low-grade astrocytoma was diagnosed in the right frontal lobe. CONCLUSION: This case emphasizes the importance of detailed history in the diagnosis of epilepsy.

A targeted endoscopic approach to chronic isolated frontal sinusitis.

OBJECTIVE: Chronic isolated frontal sinusitis occurs infrequently. In this condition, most of the ethmoid cells are well aerated and the frontal sinus is involved secondary to anatomical obstruction or inflammatory changes confined to the frontal recess. The purpose of this study was to evaluate a targeted endoscopic technique where standard anterior ethmoidectomy is unnecessary in the treatment of chronic isolated frontal sinusitis. STUDY DESIGN AND SETTING: This retrospective study was conducted in a large university-affiliated hospital and included 11 patients with chronic isolated frontal sinusitis who underwent endoscopic sinus surgery limited to the frontal sinus outflow. The ethmoid bulla was untouched in all cases. Follow-up continued for 19 to 40 months (mean 28.6 months). RESULTS: Frontal sinus outflow patency was verified in 9 patients (81.8%). Nine patients, including one with an apparent nonpatent frontal ostium, reported improvement. Two patients-one of whom had a patent frontal ostium-reported no improvement. There were no complications. CONCLUSION: Chronic isolated frontal sinusitis can be effectively treated in selected cases by a targeted endoscopic procedure, limited to reestablishment of frontal sinus outflow. EBM RATING: C-4.

Necrotizing Fasciitis of the Skull Base and Neck in a Patient with AIDS and Non-Hodgkin's Lymphoma.

Necrotizing fasciitis is a rapidly progressing, life-threatening soft tissue bacterial infection found more frequently in immunocompromised subjects and rarely in the head and neck. We report a rare case of a patient with acquired immunodeficiency syndrome (AIDS) and non-Hodgkin's lymphoma (NHL) who presented with a high fever and supraorbital cellulitis 1 week after undergoing chemotherapy. He received intravenous antibiotic therapy but soon developed dyspnea and trismus with rapid extension of the cellulitis to the face, ipsilateral infratemporal fossa (ITF), and bilateral neck. An awake tracheotomy was followed by surgical exploration and drainage and debridement of the supraorbital and ITF areas, parotid gland, and bilateral neck. He received intravenous antibiotic therapy and the surgical wound was regularly debrided for 10 days. Following a gradual recovery, the patient was discharged 2 weeks later. Early antibiotic therapy, wide surgical exploration, and a secured airway are the therapeutic mainstay for necrotizing fasciitis of the skull base and neck.