Radiologic assessment of maxillofacial, mandibular, and skull base trauma

Cranio-maxillofacial injuries affect a significant proportion of trauma patients either in isolation or concurring with other serious injuries. Contrary to maxillofacial injuries that result from a direct impact, central skull base and lateral skull base (petrous bone) fractures usually are caused by a lateral or sagittal directed force to the skull and therefore are indirect fractures. The traditional strong role of conventional images in patients with isolated trauma to the viscerocranium is decreasing. Spiral multislice CT is progressively replacing the panoramic radiograph, Waters view, and axial films for maxillofacial trauma, and is increasingly being performed in addition to conventional films to detail and classify trauma to the mandible as well. Imaging thus contributes to accurately categorizing mandibular fractures based on location, into alveolar, mandibular proper, and condylar fractures—the last are subdivided into intracapsular and extracapsular fractures. In the midface, CT facilitates attribution of trauma to the categories central, lateral, or combined centrolateral fractures. The last frequently encompass orbital trauma as well. CT is the imaging technique of choice to display the multiplicity of fragments, the degree of dislocation and rotation, or skull base involvement. Transsphenoid skull base fractures are classified into transverse and oblique types; lateral base (temporal bone) trauma is subdivided into longitudinal and transverse fractures. Supplementary MR examinations are required when a cranial nerve palsy occurs in order to recognize neural compression. Early and late complications of trauma related to the orbit, anterior cranial fossa, or lateral skull base due to infection, brain concussion, or herniation require CT to visualize the osseous prerequisites of complications, and MR to define the adjacent brain and soft tissue involvemen

Hypertrophy of the Inferior Olivary Nucleus Impacts Perception of Gravity

Interruption of the dentato-olivary projections, interconnecting the dentate nucleus (DN) and the contralateral inferior olivary nucleus (ION), is predicted to interfere with the DN’ role in estimating direction of gravity. In a patient with pendular nystagmus due to hypertrophy of the ION secondary to predominantly right-sided ponto-mesencephalic hemorrhage, perceived vertical shifted from clockwise to counter-clockwise deviations within 4 months. We hypothesize that synchronized oscillations of ION neurons induce a loss of inhibitory control, leading to hyperactivity of the contralateral DN and, as a result, to perceived vertical roll–tilt to the side of the over-active DN

Multifocal Vasculopathy Due to Varicella-Zoster Virus (VZV): Serial Analysis of VZV DNA and Intrathecal Synthesis of VZV Antibody in Cerebrospinal Fluid

Recognition of multifocal vasculopathy due to varicella-zoster virus (VZV) is often problematic. We describe a human immunodeficiency virus—infected patient who had progressive central nervous system disease for >3 months. Both VZV DNA and antibody were detected in cerebrospinal fluid (CSF) specimens; serial polymerase chain reaction analyses confirmed the diagnosis and guided the duration of therapy. Reduced ratios of VZV antibody in serum to that in CSF were also demonstrate

Radiological feature heterogeneity supports etiological diversity among patient groups in Meniere's disease

We aimed to determine the prevalence of radiological temporal bone features that in previous studies showed only a weak or an inconsistent association with the clinical diagnosis of Meniere's disease (MD), in two groups of MD patients (n = 71) with previously established distinct endolymphatic sac pathologies; i.e. the group MD-dg (ES degeneration) and the group MD-hp (ES hypoplasia). Delayed gadolinium-enhanced MRI and high-resolution CT data were used to determine and compare between and within (affected vs. non-affected side) groups geometric temporal bone features (lengths, widths, contours), air cell tract volume, height of the jugular bulb, sigmoid sinus width, and MRI signal intensity alterations of the ES. Temporal bone features with significant intergroup differences were the retrolabyrinthine bone thickness (1.04 ± 0.69 mm, MD-hp; 3.1 ± 1.9 mm, MD-dg; p < 0.0001); posterior contour tortuosity (mean arch-to-chord ratio 1.019 ± 0.013, MD-hp; 1.096 ± 0.038, MD-dg; p < 0.0001); and the pneumatized volume (1.37 [0.86] cm3, MD-hp; 5.25 [3.45] cm3, MD-dg; p = 0.03). Features with differences between the affected and non-affected sides within the MD-dg group were the sigmoid sinus width (6.5 ± 1.7 mm, affected; 7.6 ± 2.1 mm, non-affected; p = 0.04) and the MRI signal intensity of the endolymphatic sac (median signal intensity, affected vs. unaffected side, 0.59 [IQR 0.31-0.89]). Radiological temporal bone features known to be only weakly or inconsistently associated with the clinical diagnosis MD, are highly prevalent in either of two MD patient groups. These results support the existence of diverse-developmental and degenerative-disease etiologies manifesting with distinct radiological temporal bone abnormalities

Endotype-Phenotype Patterns in Meniere's Disease Based on Gadolinium-Enhanced MRI of the Vestibular Aqueduct

Two histopathological subtypes of Meniere's disease (MD) were recently described in a human post-mortem pathology study. The first subtype demonstrated a degenerating distal endolymphatic sac (ES) in the affected inner ear (subtype MD-dg); the second subtype (MD-hp) demonstrated an ES that was developmentally hypoplastic. The two subtypes were associated with different clinical disease features (phenotypes), suggesting that distinct endotype-phenotype patterns exist among MD patients. Therefore, clinical endotyping based on ES pathology may reveal clinically meaningful MD patient subgroups. Here, we retrospectively determined the ES pathologies of clinical MD patients (n = 72) who underwent intravenous delayed gadolinium-enhanced inner ear magnetic resonance imaging using previously established indirect radiographic markers for both ES pathologies. Phenotypic subgroup differences were evidenced; for example, the MD-dg group presented a higher average of vertigo attacks (ratio of vertigo patterns daily/weekly/other vs. monthly, MD-dg: 6.87: 1; MD-hp: 1.43: 1; p = 0.048) and more severely reduced vestibular function upon caloric testing (average caloric asymmetry ratio, MD-dg: 30.2% ± 30.4%; MD-hp: 13.5% ± 15.2%; p = 0.009), while the MD-hp group presented a predominantly male sex ratio (MD-hp: 0.06:1 [f/m]; MD-dg: 1.2:1 [f/m]; p = 0.0004), higher frequencies of bilateral clinical affection (MD-hp: 29.4%; MD-dg: 5.5%; p = 0.015), a positive family history for hearing loss/vertigo/MD (MD-hp: 41.2%; MD-dg: 15.7%; p = 0.028), and radiographic signs of concomitant temporal bone abnormalities, i.e., semicircular canal dehiscence (MD-hp: 29.4%; MD-dg: 3.6%; p = 0.007). In conclusion, this new endotyping approach may potentially improve the diagnosis, prognosis and clinical decision-making for individual MD patients

Radiological Configuration of the Vestibular Aqueduct Predicts Bilateral Progression in Meniere's Disease

Objective: Meniere's disease (MD) progresses from unilateral to bilateral disease in up to 50% of patients, often chronically and severely impairing balance and hearing functions. According to previous studies, 91% of bilateral MD patients demonstrate bilateral hypoplasia of the endolymphatic sac (ES) upon histological and radiological examination of their inner ears. Here, we seek to validate a radiological marker for ES hypoplasia that predicts the risk for future progression to bilateral MD in individual patients.Methods: Patients with unilateral MD and radiological evidence for ES hypoplasia in either the clinically affected inner ear (cohort MD$_{uni}$-hp$_{uni}$) or both inner ears (cohort MD$_{uni}$-hp$_{bi}$) were included. Given our hypothesis that ES hypoplasia critically predisposes the inner ear to MD, we expected progression to bilateral MD only in the MD$_{uni}$-hp$_{bi}$ cohort. To investigate eventual progression to bilateral MD, clinical, audiometric, and imaging data were retrospectively collected over follow-up periods of up to 31 years.Results: A total of 44 patients were included in the MD-hp$_{uni}$ (n = 15) and MD$_{uni}$-hp$_{bi}$ (n = 29) cohorts. In line with our radiology-based predictions, none (0/15) of the MD-hp$_{uni}$ patients exhibited progression to bilateral MD, whereas 20/29 (69%) MD-hp$_{bi}$ patients have already progressed to bilateral MD. Using the Kaplan–Meier estimator, bilateral disease progression would be observed in 100% of MD-hp$_{bi}$ patients 31 years after the initial diagnosis with an estimated median time to bilateral progression of 12 years. The nine MD-hp$_{bi}$ patients who, so far, remained with unilateral disease demonstrated a median time since initial (unilateral) MD diagnosis of only 6 years and are thus still expected to progress to bilateral disease.Conclusion: Progression to bilateral MD adheres to predictions based on the radiological presence or absence of ES hypoplasia. This prognostic tool, if validated by prospective long-term studies, will provide clinically relevant information about a patient's future disease burden and will help to select more personalized treatment regimens

Random number generation deficits in patients with multiple sclerosis: Characteristics and neural correlates

Human subjects typically deviate systematically from randomness when attempting to produce a sequence of random numbers. Despite an increasing number of behavioral and functional neuroimaging studies on random number generation (RNG), its structural correlates have never been investigated. We set out to fill this gap in 44 patients with multiple sclerosis (MS), a disease whose impact on RNG has never been studied. The RNG task required the paced (1 Hz) generation of the numbers from 1 to 6 in a sequence as random as possible. The same task was administered in 39 matched healthy controls. To assess neuroanatomical correlates such as cortical thickness, lesion load and third ventricle width, all subjects underwent high-resolution structural MRI. Compared to controls, MS patients exhibited an enhanced tendency to arrange consecutive numbers in an ascending order (“forward counting”). Furthermore, patients showed a higher susceptibility to rule breaks (producing out-of-category digits like 7) and to skip beats of the metronome. Clinico-anatomical correlation analyses revealed two main findings: First, increased counting in MS patients was associated with higher cortical lesion load. Second, increased number of skipped beats was related to widespread cortical thinning. In conclusion, our test results illustrate a loss of behavioral complexity in the course of MS, while the imaging results suggest an association between this loss and cortical pathology

Unexplained peripheral neuropathic pain and/or stroke

Fabry disease is a rare X-linked lysosomal storage disorder caused by the absence or deficiency of the hydrolase alpha-galactosidase A activity. As a consequence, accumulation of globotriaosylceramide occurs in a wide variety of cells throughout the human body. Specific gene mutations determine disease severity and different phenotypes. Fabry disease is a multisystemic disease with nonspecific initial mani festations. Neuropathic pain and acroparaesthesia are one of the earliest symptoms, already reported in childhood or adolescence. Later signs and symptoms involve the heart, kidney and brain, resulting in life-threatening complications such as cardiac and renal failure as well as cerebral strokes. Early treatment initiation can ameliorate disease progression and potentially prevents long-term complications. Based on its diverse and nonspecific manifestation, it can take up to 15 years between the onset of the first symptoms and the final diagnosis of Fabry disease. Recognition of early symptoms, such as neuropathic pain and acroparaesthesia, and considering Fabry disease in young patients with stokes, is important. As such, neurologists may play a key role in early diagnosis of this disease

Cerebellar Rebound Nystagmus Explained as Gaze-Evoked Nystagmus Relative to an Eccentric Set Point: Implications for the Clinical Examination

A brain stem/cerebellar neural integrator enables stable eccentric gaze. Cerebellar loss-of-function can cause an inability to maintain gaze eccentrically (gaze-evoked nystagmus). Moreover, after returning gaze to straight ahead, the eyes may drift toward the prior eye position (rebound nystagmus). Typically, gaze-evoked nystagmus decays during continuously held eccentric gaze. We hypothesized this adaptive behavior to be prerequisite for rebound nystagmus and thus predicted a correlation between the velocity decay of gaze-evoked nystagmus and the initial velocity of rebound nystagmus. Using video-oculography, eye position was measured in 11 patients with cerebellar degeneration at nine horizontal gaze angles (15° nasal to 25° temporal) before (baseline), during, and after attempted eccentric gaze at ± 30° for 20 s. We determined the decrease of slow-phase velocity at eccentric gaze and the slow-phase velocity of the subsequent rebound nystagmus relative to the baseline. During sustained eccentric gaze, eye drift velocity of gaze-evoked nystagmus decreased by 2.40 ± 1.47°/s. Thereafter, a uniform change of initial eye drift velocity relative to the baseline (2.40 ± 1.35°/s) occurred at all gaze eccentricities. The velocity decrease during eccentric gaze and the subsequent uniform change of eye drift were highly correlated (R$^{2}$ = 0.80, p < 0.001, slope = 1.09). Rebound nystagmus can be explained as gaze-evoked nystagmus relative to a set point (position with least eye drift) away from straight-ahead eye position. To improve detection at the bedside, we suggest testing rebound nystagmus not at straight-ahead eye position but at an eccentric position opposite of prior eccentric gaze (e.g., 10°), ideally using quantitative video-oculography to facilitate diagnosis of cerebellar loss-of-function

Durable Control of Metastatic AKT1-Mutant WHO Grade 1 Meningothelial Meningioma by the AKT Inhibitor, AZD5363

High-throughput analyses have revealed the presence of activating mutations in the AKT1 gene in a subpopulation of meningiomas. We report a female patient with multiple intracranial tumor manifestations and histologically verified meningotheliomatous meningioma in the lung. The tumor was continuously growing at multiple sites despite six surgical resections, radiotherapy, and two lines of systemic therapy. Following detection of an AKT1E17K mutation in three independent tumor samples by sequencing, treatment with AZD5363, a selective AKT inhibitor, was initiated. Ex vivo cultured meningioma cells exhibited sensitivity to the drug as shown by pAKT accumulation on immunoblots. Treatment with AZD5363 resulted, for the first time, in stable disease and minor radiographic response. The patient has been on that treatment for more than one year with ongoing clinical and radiographic response. This is the first report of an AKT1-mutant meningioma responding to AKT inhibition, suggesting that molecular screening may result in clinical benefit