NUBPL mitochondrial disease: new patients and review of the genetic and clinical spectrum.

BACKGROUND: The nucleotide binding protein-like (NUBPL) gene was first reported as a cause of mitochondrial complex I deficiency (MIM 613621, 618242) in 2010. To date, only eight patients have been reported with this mitochondrial disorder. Five other patients were recently reported to have NUBPL disease but their clinical picture was different from the first eight patients. Here, we report clinical and genetic findings in five additional patients (four families). METHODS: Whole exome sequencing was used to identify patients with compound heterozygous NUBPL variants. Functional studies included RNA-Seq transcript analyses, missense variant biochemical analyses in a yeast model (Yarrowia lipolytica) and mitochondrial respiration experiments on patient fibroblasts. RESULTS: The previously reported c.815-27T>C branch-site mutation was found in all four families. In prior patients, c.166G>A [p.G56R] was always found in cis with c.815-27T>C, but only two of four families had both variants. The second variant found in trans with c.815-27T>C in each family was: c.311T>C [p.L104P] in three patients, c.693+1G>A in one patient and c.545T>C [p.V182A] in one patient. Complex I function in the yeast model was impacted by p.L104P but not p.V182A. Clinical features include onset of neurological symptoms at 3-18 months, global developmental delay, cerebellar dysfunction (including ataxia, dysarthria, nystagmus and tremor) and spasticity. Brain MRI showed cerebellar atrophy. Mitochondrial function studies on patient fibroblasts showed significantly reduced spare respiratory capacity. CONCLUSION: We report on five new patients with NUBPL disease, adding to the number and phenotypic variability of patients diagnosed worldwide, and review prior reported patients with pathogenic NUBPL variants.

A novel, noninvasive, predictive epilepsy biomarker with clinical potential.

A significant proportion of temporal lobe epilepsy (TLE), a common, intractable brain disorder, arises in children with febrile status epilepticus (FSE). Preventative therapy development is hampered by our inability to identify early the FSE individuals who will develop TLE. In a naturalistic rat model of FSE, we used high-magnetic-field MRI and long-term video EEG to seek clinically relevant noninvasive markers of epileptogenesis and found that reduced amygdala T2 relaxation times in high-magnetic-field MRI hours after FSE predicted experimental TLE. Reduced T2 values likely represented paramagnetic susceptibility effects derived from increased unsaturated venous hemoglobin, suggesting augmented oxygen utilization after FSE termination. Indeed, T2 correlated with energy-demanding intracellular translocation of the injury-sensor high-mobility group box 1 (HMGB1), a trigger of inflammatory cascades implicated in epileptogenesis. Use of deoxyhemoglobin-sensitive MRI sequences enabled visualization of the predictive changes on lower-field, clinically relevant scanners. This novel MRI signature delineates the onset and suggests mechanisms of epileptogenesis that follow experimental FSE.

Case 220: Neurocutaneous Melanosis.

History A 3-month-old boy presented with new onset of seizure that subsided when he arrived at our institution. There was no reported fever or family history of seizure. Physical examination did not reveal any neurologic abnormalities. Multiple skin lesions of varying sizes were identified on the scalp, trunk, and extremities and were reported to have been present since birth. Laboratory test results were normal. Magnetic resonance (MR) imaging of the brain was performed.

PACS used while on-call: a national survey of radiology program directors and chief residents.

The aim of this study was to determine the prevalence of different diagnostic image viewing platforms used by radiologists while on-call, and to assess the opinions and preferences of radiology program directors and chief residents regarding their use. An online survey was sent electronically to radiology residency program directors and chief residents via the Association of University Radiologists. Forty-two radiology program directors and 25 chief residents completed the survey, yielding response rates of 24.9 and 8.5 %, respectively. From the survey results, 10 different Picture Archiving Communications Systems (PACS) were identified; GE (25 %), Philips (17 %), and Agfa Impax (15 %) were the most prevalent. Interestingly, only 5 % of all respondents use a secondary "Digital Imaging and Communications in Medicine" viewer for on-call studies. Perceptions of PACS functionality were generally neutral to weakly positive. Most respondents strongly agreed that it is important to have a single integrated PACS for viewing on-call studies and agreed that the PACS should be integrated into the Electronic Medical Records (EMR). The overwhelming majority of respondents use their institution's PACS while on-call. The results show there is still a wide variety of PACS platforms used by different institutions; however, GE, Phillips, and Agfa were some of the most prevalent. Most radiologists surveyed have neutral to slightly positive perceptions about the functionality and ease of use of their PACS. Finally, while radiologists agree that PACS should be integrated with EMR, only 53 % of respondents currently have this arrangement.

Predicting stroke evolution: comparison of susceptibility-weighted MR imaging with MR perfusion.

OBJECTIVES: To investigate the ability of susceptibility-weighted imaging (SWI) to predict stroke evolution in comparison with perfusion-weighted imaging (PWI). METHODS: In a retrospective analysis of 15 patients with non-lacunar ischaemic stroke studied no later than 24 h after symptom onset, we used the Alberta Stroke Program Early CT Score (ASPECTS) to compare lesions on initial diffusion-weighted images (DWI), SWI, PWI and follow-up studies obtained at least 5 days after symptom onset. The National Institutes of Health Stroke Scale scores at entry and stroke risk factors were documented. The clinical-DWI, SWI-DWI and PWI-DWI mismatches were calculated. RESULTS: SWI-DWI and mean transit time (MTT)-DWI mismatches were significantly associated with higher incidence of infarct growth (P = 0.007 and 0.028) and had similar ability to predict stroke evolution (P = 1.0). ASPECTS values on initial DWI, SWI and PWI were significantly correlated with those on follow-up studies (P ≤ 0.026) but not associated with infarct growth. The SWI ASPECTS values were best correlated with MTT ones (ρ = 0.8, P < 0.001). CONCLUSIONS: SWI is an alternative to PWI to assess penumbra and predict stroke evolution. Further prospective studies are needed to evaluate the role of SWI in guiding thrombolytic therapy. Key Points • SWI can provide perfusion information comparable to MTT • SWI-DWI mismatch can indicate ischaemic penumbra • SWI-DWI mismatch can be a predictor for stroke evolution.

Sequence-specific MR imaging findings that are useful in dating ischemic stroke.

Patients may present to the hospital at various times after an ischemic stroke. Many present weeks after a neurologic deficit has occurred, as is often the case with elderly patients and those in a nursing home. The ability to determine the age of an ischemic stroke provides useful clinical information for the patient, his or her family, and the medical team. Many times, perfusion imaging is not performed, and pulse sequence-specific magnetic resonance (MR) imaging findings may help determine the age of the infarct. The findings seen at apparent diffusion coefficient mapping and diffusion-weighted, fluid-attenuated inversion recovery (FLAIR) and unenhanced and contrast material-enhanced T1- and T2-weighted gradient-echo and susceptibility-weighted MR imaging may help determine the relative age of a cerebral infarct. Strokes may be classified and dated as early hyperacute, late hyperacute, acute, subacute, or chronic. Recent data indicate that in many patients with restricted diffusion and no change on FLAIR images, it is more likely than was initially thought that the stroke is less than 6 hours old. The time window to administer intravenous tissue plasminogen activator is currently 4.5 hours from the time when the patient was last seen to be normal, and for anterior circulation strokes, the time window for administering intraarterial tissue plasminogen activator is 6 hours from when the patient was last seen to be normal. For this reason, accurate dating is important in patients with ischemic stroke.

A system architecture for sharing de-identified, research-ready brain scans and health information across clinical imaging centers.

Progress in our understanding of brain disorders increasingly relies on the costly collection of large standardized brain magnetic resonance imaging (MRI) data sets. Moreover, the clinical interpretation of brain scans benefits from compare and contrast analyses of scans from patients with similar, and sometimes rare, demographic, diagnostic, and treatment status. A solution to both needs is to acquire standardized, research-ready clinical brain scans and to build the information technology infrastructure to share such scans, along with other pertinent information, across hospitals. This paper describes the design, deployment, and operation of a federated imaging system that captures and shares standardized, de-identified clinical brain images in a federation across multiple institutions. In addition to describing innovative aspects of the system architecture and our initial testing of the deployed infrastructure, we also describe the Standardized Imaging Protocol (SIP) developed for the project and our interactions with the Institutional Review Board (IRB) regarding handling patient data in the federated environment.

Magnetic Resonance Imaging Findings in High School Football Players: Brain and Cervical Spine.

Football exposes its players to traumatic brain, neck, and spinal injury. It is unknown whether the adolescent football player develops imaging abnormalities of the brain and spine that are detectable on magnetic resonance imaging (MRI). The objective of this observational study was to identify potential MRI signatures of early brain and cervical spine (c-spine) injury in high school football players. Eighteen football players (mean age, 17.0 ± 1.5 years; mean career length, 6.3 ± 4.0 years) had a baseline brain MRI, and 7 had a follow-up scan 9-42 months later. C-spine MRIs were performed on 11 of the 18 subjects, and 5 had a follow-up scan. C-spine MRIs from 12 age-matched hospital controls were also retrospectively retrieved. Brain MRIs were reviewed by a neuroradiologist, and no cerebral microbleeds were detected. Three readers (a neuroradiologist, a neurosurgeon, and an orthopedic spine surgeon) studied the cervical intervertebral discs at six different cervical levels and graded degeneration using an established five-grade scoring system. We observed no statistically significant difference in disc degeneration or any trend toward increased disc degeneration in the c-spine of football players as compared with age-matched controls. Further research is needed to validate our findings and better understand the true impact of contact sports on young athletes.

Primary leptomeningeal plasmablastic lymphoma.

Lymphomas that develop in human immunodeficiency virus (HIV) infected patients are predominantly aggressive B-cells lymphomas. The most common HIV-associated lymphomas include Burkitt lymphoma, diffuse large B-cell lymphoma (that often involves the CNS), primary effusion lymphoma, and plasmablastic lymphoma (PBL). Of these, PBL is relatively uncommon and displays a distinct affinity for presentation in the oral cavity. In this manuscript we report a previously undescribed primary leptomeningeal form of PBL in a patient with acquired immunodeficiency syndrome. A 40-year-old HIV positive man presented with acute onset confusion, emesis, and altered mental status. Lumbar puncture showed numerous nucleated cells with atypical plasmocyte predominance. CSF flowcytometry showed kappa restriction with CD8 and CD38 positivity and negative lymphocyte markers, while the MRI showed diffuse leptomeningeal enhancement. As the extensive systemic work-up failed to reveal any disease outside the brain, an en bloc diagnostic brain and meningeal biopsy was performed. The biopsy specimen showed sheets of plasmacytoid cells with one or more large nuclei, prominent nuclear chromatin, scattered mitoses, and abundant cytoplasm, highly suggestive of plasmablastic lymphoma. HIV-associated malignancies have protean and often confusing presentations, which pose diagnostic difficulties posed to the practicing neurological-surgeons. Even in cases where an infectious cause is suspected for the meningeal enhancement, neoplastic involvement should be considered, and cytology and flow-cytometry should be routinely ordered on the CSF samples.

Asymmetrically severe internal auditory canal hypoplasia: A case report.

We present a case of an otherwise healthy 20-month-old with congenital sensorineural hearing loss. CT and MR imaging demonstrated bilateral asymmetrically severe hypoplasia of the internal auditory canals and vestibulocochlear nerves. Additional developmental inner ear anomalies were present in this patient, including unilateral semicircular canal hypoplasia and suspected bilateral cochlear hypoplasia. The patient retained normal facial nerve function bilaterally. We highlight the current research and understanding of congenital IAC abnormalities.

CNS viruses--diagnostic approach.

Diagnosis of CNS viral infections is challenging; yet, significant progress in laboratory diagnosis of CNS infections has come through applications of serology and polymerase chain reaction (PCR) to CSF and tissues. Advances in molecular and laboratory techniques, together with neuroimaging, epidemiologic, and surveillance efforts, are yielding greater success in CNS viral diagnosis and treatment.

The effect of bevacizumab (Avastin) on neuroimaging of brain metastases.

BACKGROUND: Bevacizumab is FDA approved to treat colon cancer and is currently used off label for metastatic breast, kidney, and lung cancers. Bevacizumab is a monoclonal antibody that binds to, and inactivates, VEGF and is believed to be antiangiogenic. CASE DESCRIPTION: The authors report the case of a 54-year-old woman with metastatic infiltrating ductal breast carcinoma who developed left occipital and right parietal intraaxial contrast-enhancing masses on surveillance magnetic resonance imaging (MRI). After surgical resection, she was placed on bevacizumab for control of systemic disease. Six months later, a nonenhancing right occipital lesion was detected on MRI. After stopping bevacizumab therapy, the patient underwent microsurgical resection of the lesion. Histopathologic examination was consistent with metastatic breast cancer indistinguishable from her previously resected enhancing brain metastasis. Six weeks after stopping bevacizumab therapy and 3 weeks after microsurgical resection, a new contrast-enhancing mass was noted on magnetic resonance in the right temporal lobe. CONCLUSION: This case is unique in that we have neuroimaging on prebevacizumab, concurrent bevacizumab, and postbevacizumab brain metastases in the same patient with a single cancer primary, thus, assuring that alterations in neuroimaging characteristics are consistent with bevacizumab effect. As an internal control, it provides strong support for the premise that bevacizumab therapy can confound the diagnosis of brain metastases because of its effect on tumor enhancement.

Extramedullary hematopoeisis within a convexity meningioma.

BACKGROUND: Hematopoiesis outside the bone marrow is known to occur in patients with severe anemia, leukemia, polycythemia, or myelofibrosis, and in patients affected by chronic poisoning by marrow-toxic substances. CASE DESCRIPTION: A 66-year-old right-handed man complained of 4 days of terrible right-sided, sharp, and shooting headache for which he saw his primary care provider. Routine laboratory examination showed a WBC count of 30800/microL. Neuroimaging showed a large, right frontotemporal, extra-axial, heterogeneously enhancing, dural based mass with associated recent intramural hemorrhage with evidence of midline shift and uncal herniation. The mass was resected using a right-sided extended craniotomy with anterior fossa and middle fossa approach. A hematoxylin-eosin-stained biopsy specimen showed whorls of tumor cells, diagnostic of a meningioma. Interspersed within the tumor bulk were nucleated RBCs, representing areas of extramedullary erythropoiesis within a meningioma. Flow cytometric evaluation confirmed the clinical suspicion of an underlying chronic lymphocytic leukemia. CONCLUSION: Occurrence of extramedullary hematopoiesis within a meningioma is extremely rare. Various theories may explain the occurrence of extramedullary hematopoiesis occurring within a meningioma in our patient, such as hematopoietic differentiation of multipotent mesenchymal tumor cells; direct extension of hematopoietic activity from the neighboring marrow cavity; displacement from bone marrow of stem cells that settle and develop in tissues where capillaries and blood vessels proliferate, such as a meningioma; or congenital heterotopia of totipotent connective tissue cells, which, under certain circumstances, may transform into hematopoietic tissue.

Malignant Orbital Meningioma Originating from the Frontal Lobe.

PURPOSE OF THE STUDY: Orbital meningiomas are typically benign tumors, most commonly originating from the dura of the sphenoid wing or the optic nerve sheath. PROCEDURES: We describe an unusual case of a malignant meningioma originating from the frontal lobe that ultimately produced orbital and distant metastases. RESULTS AND CONCLUSIONS: Orbital invasion by the meningioma was preceded by multiple incomplete resections, which may have facilitated access to the orbit. The present case serves to remind clinicians that surgical resection of aggressive, recurrent frontal lobe meningiomas may facilitate subsequent penetration of surrounding structures, particularly by tumors that demonstrate bone-destructive properties.

Lemierre syndrome complicated by cavernous sinus thrombosis, the development of subdural empyemas, and internal carotid artery narrowing without cerebral infarction. Case report.

Lemierre syndrome is an extremely rare complication of mild-to-moderate pharyngeal infections. The authors present an unusual case of Lemierre syndrome in a 16-year-old boy with cavernous sinus thrombosis and right internal carotid artery narrowing without neurological sequelae, right subdural empyema, and cerebritis in the right temporal and occipital lobes. Neuroimaging also demonstrated right jugular vein thrombosis. Cultures of samples from the blood proved positive for the presence of Fusobacterium necrophorum. The patient underwent unilateral tonsillectomy, drainage of the peritonsillar abscess, and a myringotomy on the right side. Postoperatively the patient was treated conservatively with antibiotic therapy resulting in an excellent outcome.

Intraventricular cryptococcal cysts masquerading as racemose neurocysticercosis.

BACKGROUND: Cryptococcal infections of the CNS are infrequent in immunocompetent hosts. When present, they usually present as meningitis and hydrocephalus or as fungal masses called cryptococcomas. We report a case in which intraventricular cryptococcal cysts clinically and radiologically simulated the racemose form of neurocysticercosis. CASE DESCRIPTION: A 23-year-old man presented to the emergency department with a 1-week history of severe headache, dizziness, nausea, vomiting, and some lethargy. A computed tomography scan revealed significant hydrocephalus. The patient was admitted to the hospital and immediately underwent a right ventriculostomy tube placement. CSF examination showed a meningitic pattern. Magnetic resonance imaging, including FLAIR images, showed multiple large cysts in the temporal horns of both lateral ventricles in addition to hydrocephalus. When an endoscopic left temporal cyst fenestration failed to decompress his trapped right temporal horn, he underwent placement of a left lateral ventricle to peritoneal shunt and a right temporal cyst to peritoneal shunt. ELISA test results for HIV-1 and -2 antibodies in the patient's serum were negative. His CD4 and CD8 counts were within normal limits. Multiple tests for CSF anticysticercal antibody using IgG ELISA gave unequivocally negative results. Latex agglutination tests detected Cryptococcus neoformans antigen in his CSF in titers of 1:1024, which progressively decreased in response to antifungal therapy. The patient underwent treatment with IV amphotericin B for 7 weeks, IV 5-FC for 2 weeks, and oral fluconazole for 5 weeks. At discharge, 3 consecutive CSF cultures were negative for bacteria and fungi. His neurologic status returned to baseline. CONCLUSIONS: Cryptococcal CNS infections in immunocompetent hosts can mimic the intraventricular form of racemose neurocysticercosis. Distinguishing between the two is essential because the medical management of the 2 conditions is distinct from each other.

Bifid mandibular condyle: CT and MR imaging appearance in two patients: case report and review of the literature.

We describe two cases of a bifid mandibular condyle. The first case is a 48-year-old woman with headaches and a pain and clicking sensation in her right jaw during mastication. The second case is an asymptomatic 17-year-old woman with a history of bilateral microtia and hemifacial microsomia. In both patients, the bifid condyle was first identified by CT and affected the temporomandibular joint. The imaging findings of both patients' bifid mandibular condyles led us to conclude that both patients likely had an abnormal development of the mandibular condyles. We believe that an intervening fibrous or vascular structure may have split the condyle into two heads.

Visual field changes as an early indicator of glioblastoma multiforme progression: two cases of functional vision changes before MRI detection.

Glioblastoma multiforme is an aggressive tumor associated with a high rate of recurrence even after maximal therapy. In a disease with poor prognosis and rapid deterioration, early detection of tumor progression is necessary to make timely treatment decisions or to initiate end of life care. We identify two cases where Humphrey visual field testing predated magnetic resonance imaging and positron emission tomography findings of tumor progression by months in glioblastoma multiforme. New or worsening visual field defects may indicate signs of tumor progression in glioblastoma multiforme and should prompt further investigation.