Exon skipping restores dystrophin expression, but fails to prevent disease progression in later stage dystrophic dko mice.

Antisense therapy with both chemistries of phosphorodiamidate morpholino oligomers (PMOs) and 2'-O-methyl phosphorothioate has demonstrated the capability to induce dystrophin expression in Duchenne muscular dystrophy (DMD) patients in phase II-III clinical trials with benefit in muscle functions. However, potential of the therapy for DMD at different stages of the disease progression is not understood. In this study, we examined the effect of peptide-conjugated PMO (PPMO)-mediated exon skipping on disease progression of utrophin-dystrophin-deficient mice (dko) of four age groups (21-29, 30-39, 40-49 and 50+ days), representing diseases from early stage to advanced stage with severe kyphosis. Biweekly intravenous (i.v.) administration of the PPMO restored the dystrophin expression in nearly 100% skeletal muscle fibers in all age groups. This was associated with the restoration of dystrophin-associated proteins including functional glycosylated dystroglycan and neuronal nitric synthase. However, therapeutic outcomes clearly depended on severity of the disease at the time the treatment started. The PPMO treatment alleviated the disease pathology and significantly prolonged the life span of the mice receiving treatment at younger age with mild phenotype. However, restoration of high levels of dystrophin expression failed to prevent disease progression to the mice receiving treatment when disease was already at advanced stage. The results could be critical for design of clinical trials with antisense therapy to DMD.

MR of post traumatic spinal cord lesions. Unexpected improvement of hemorrhagic lesions.

Fifteen patients who sustained spinal cord trauma were evaluated by MR within 72 hours of injury. Nine patients had hemorrhagic and six had nonhemorrhagic traumatic spinal cord lesions. Three patients with hemorrhagic and all six patients with nonhemorrhagic lesions showed some degree of neurological improvement on follow-up examinations. In two of the three patients with hemorrhagic lesions who improved, the hemorrhage was extensive. This supports the observation that hemorrhagic lesions are not always associated with a poor clinical outcome.

Intrinsic cervical spinal cord deformation on MRI: "the distorted 'H' sign".

Extrinsic and intrinsic pathologic processes involving the spinal cord can affect its gross morphologic appearance. Contour-related abnormalities of the spinal cord can be determined by both noninvasive and invasive imaging techniques. Detailing internal dysmorphism of the spinal cord is more difficult to determine because the internal architecture of the cord is not usually visualized. Now magnetic resonance (MR) imaging can readily demonstrate the central "H" configuration of the normal spinal gray matter on axial T2* gradient-recall echo pulse sequences; thus, it should also be capable of demonstrating distortions of it. We initially reviewed 55 abnormal cervical spine 1.5-T MR imaging studies. Of 37 large lesions, 31 deformed the "H" whereas 18 small lesions did not. To compare potential differences in visualization of the "H" by MR scanners of different field strengths (1.5-0.5 T), a total of 125 additional patients were reviewed at different State University of New York (SUNY) sites. Visualization of the "H" varied from 51.4% at 1.5 T to 18.4% at 0.5 T. As resolution of the spinal cord increases on MR imaging, it becomes possible to more accurately map the altered cord "interior," which may have a detectable clinical (neurologic) counterpart.

Percutaneous CT-guided aspiration of deep neck abscesses.

Four patients with deep neck or retropharyngeal abscesses underwent CT-guided aspiration and drainage from either of two percutaneous approaches. Percutaneous drainage contributed to prompt and/or dramatic clinical responses in all four patients by effecting decompression of the abscess cavities and by improving the ability to assess infectious organisms. There were no complications in this small group. Precutaneous drainage obviated more traditional invasive surgery.

A rare case of cerebellar glioblastoma multiforme in childhood: MR imaging.

Glioblastoma multiforme is a highly malignant brain neoplasm that is very rarely discovered in childhood but accounts for approximately 17% of intracranial tumors in the adult. Only approximately 25 children with glioblastoma multiforme in the cerebellum have been described in the literature. We report on a 4 1/2-year-old girl with this tumor in the cerebellar hemisphere and discuss the magnetic resonance imaging findings.

Acute internal jugular vein thrombosis associated with pseudoabscess of the retropharyngeal space.

We present four patients in whom evidence of edema or a pseudomass in the retropharyngeal space was found on CT scans obtained after thrombosis of the internal jugular vein. The clinical condition of one patient led to surgery, which documented the sterility of the retropharyngeal space despite the CT appearance of an inflammatory process. The CT findings, which are confusing initially, are found to be typical in retrospect.

Demyelinating and gliotic cerebellar lesions in Langerhans cell histiocytosis.

PURPOSE: To describe the involvement of the cerebellum by a gliotic and demyelinating process in Langerhans cell histiocytosis. METHODS: A retrospective analysis of all (N = 30) cases of Langerhans cell histiocytosis followed at our institution since 1975 yielded four patients with CT and/or MR evidence of cerebellar abnormalities. RESULTS: Four patients manifested strikingly similar findings of symmetric nonenhancing hypodensities in the dentate nuclei region of the cerebellum, which were hypointense on short-repetition-time/short-echo-time MR and hyperintense on long-repetition-time/long-echo-time MR. Biopsy in one patient yielded areas of demyelination, cell loss, and gliosis without histiocytic infiltration. CONCLUSION: Langerhans cell histiocytosis involves the cerebellum in a specific and poorly understood manner. Lesions on imaging may precede clinical findings by years. Lesions may occur in patients who have never experienced radiation therapy and may act as a marker for eventual central nervous system deterioration.

Neurocutaneous melanosis presenting as an intradural mass of the cervical canal: magnetic resonance features and the presence of melanin as a clue to diagnosis: case report.

We present a case of neurocutaneous melanosis in a 1-year-old child who presented with progressive quadriparesis created by an infiltrating extra-axial neoplastic melanin-producing tumor at the foramen magnum. This extensive intra-arachnoid mass filled the basal cisterns of the brain and surrounded the upper cervical cord. An imaging clue to the diagnosis was apparent as T1-weighted shortening on magnetic resonance in the pia and/or cortex of the cerebellar folia, suggesting the presence of melanin.

Antemortem diagnosis of Baló concentric sclerosis: correlative MR imaging and pathologic features.

PURPOSE: To report a case of a rare demyelinating disease called Baló concentric sclerosis. MATERIALS AND METHODS: A 32-year-old woman had left hemiparesis that progressed to hemiplegia, hemihypesthesia, and left hemianopsia. Laboratory evaluation was notable only for a mildly elevated erythrocyte sedimentation rate and an elevated level of myelin basic protein in cerebrospinal fluid. RESULTS: The antemortem diagnosis was made on the basis of magnetic resonance (MR) imaging of the brain, which showed numerous areas of concentric demyelination alternating with "spared" white matter. With the exception of a temporary improvement with high-dosage intravenous steroid therapy, the clinical course was monophasic and relentless, leading to death approximately 1 year after the onset of symptoms. Pathologic examination helped confirm the diagnosis. CONCLUSION: Because MR imaging shows alternating ringlike lesions involving the deep and superficial white matter, which correspond to pathologic findings, it may play a central role in antemortem diagnosis of this rare disease, leaving more invasive diagnostic procedures for evaluation of equivocal cases.

The importance of intimacy to men living in a nursing home.

Intimacy and its contribution to life satisfaction have not been explored among institutionalized elders. We studied residents of a Veterans Affairs nursing home and assessed cognitive and physical function, life satisfaction, and importance of intimacy. The Folstein Mini-Mental State, Barthel Index, Life Satisfaction Index-Z, and a series of vignettes were used to assess each domain. Vignettes depicted various scenarios (e.g., recent admission to a nursing home, notification of diagnosis of a terminal disease), and asked the subject to rate the importance of intimate social, intellectual, emotional, or physical interactions. Social intimacy was rated as most important, followed by nonsexual physical, intellectual, emotional, and finally, sexual-physical intimacy (social vs. sexual-physical, p = 0.0013). In addition, social (rs = .299, p = 0.023), nonsexual physical (rs = .312, p = 0.019), and intellectual (rs = .382, p = 0.005) intimacy were associated with life satisfaction. Nursing home care providers can enhance resident quality of life through social, intellectual, and nonsexual physical interactions even when the underlying medical, physical, or cognitive deficit cannot be ameliorated.

Sinus histiocytosis with massive lymphadenopathy: a case of simultaneous upper respiratory tract and CNS disease without lymphadenopathy.

The authors describe a 20-year-old man who initially developed an intradural mass in the upper cervical region and subsequently presented with nasal/paranasal sinus and posterior fossa masses, well demonstrated by CT and MR. Histopathology demonstrated dense fibrous tissue, aggregates of histiocytes with round to oval vesicular nuclei, and other features diagnostic of Rosai-Dorfman disease; a right nasal biopsy prior to surgery showed similar microscopic findings.

MR of progressive neurodegenerative change in treated Menkes' kinky hair disease.

MR examinations of a male child with Menkes' kinky hair disease, a genetic disorder of copper metabolism, at four months and 30 months, document the progression of neurodegenerative changes despite parenteral copper therapy. These changes include severe cortical and cerebellar atrophy, deranged cerebral vasculature, and subdural fluid collection.

Congenital central nervous system anomalies.

Magnetic resonance imaging, because of its multiplanar capabilities and exquisite contrast differentiation, has risen above all other forms of in vivo imaging for the classification and determination of congenital central nervous system (CNS) anomalies. We briefly discuss pertinent aspects of CNS embryology and, using a recently proposed classification of central nervous system anomalies, present examples of a spectrum of abnormalities that one may encounter in practice. These anomalies include: the Chiari malformations, encephaloceles, holoprosencephaly, septooptic dysplasia, Dandy-Walker variant, hydranencephaly, phakomatoses, schizencephaly, agyria or pachygyria, and dysgenesis of the corpus callosum.

Viral and bacterial organisms associated with acute pharyngitis in a school-aged population.

To investigate the causes and clinical characteristics of acute pharyngitis among school-aged children (4 to 18 years), we obtained throat cultures for respiratory viruses, Mycoplasma pneumoniae, group A streptococcus, and Chlamydia trachomatis from 320 patients with sore throat and 308 controls without respiratory complaints. The study was conducted from January to April 1985 in a private pediatric practice in central New York State. Sixty percent of the patients and 26% of the control subjects had positive cultures for at least one organism. Forty percent of patients had positive cultures for group A streptococcus, compared with 11.9% of the controls. Fifty (16%) patients had positive viral cultures, compared with eight (2.6%) controls; the predominant viral isolate was influenza A Philippines. Patients infected with influenza A were significantly more likely to complain of cough and hoarseness, and were less likely to have pharyngeal exudate or tender cervical adenopathy, than were patients who had positive cultures for group A streptococcus. Although 49 (15.8%) patients with acute pharyngitis had cultures positive for M. pneumoniae, 53 (17.6%) asymptomatic controls were also had M. pneumoniae-positive cultures. Thus detection of M. pneumoniae in the throat of school-aged children with pharyngitis may not be sufficient to establish a diagnosis of disease caused by this organism. C. trachomatis was not isolated from any patient or control.

New York City medium for enhanced recovery of Mycoplasma pneumoniae from clinical specimens.

Modified New York City (MNYC) medium and PPLO medium without methylene blue (PPLO agar) were compared for their ability to support the growth of Mycoplasma pneumoniae from clinical specimens. Pharyngeal specimens were collected from 1,070 college students who visited the Syracuse University Student Health Center. Of these patients, 623 were symptomatic for respiratory infection, and the remaining 447 were asymptomatic for respiratory illness. Throat swabs were inoculated into PPLO broths, and these broths were subcultured onto MNYC medium and PPLO agar after 3 and 14 days of incubation. A total of 222 (20.7%) clinical isolates of M. pneumoniae were recovered on these solid media, with the majority of the isolates (196) recovered from symptomatic patients. All isolates grew on MNYC medium, whereas five isolates failed to grow on PPLO agar. All isolates of M. pneumoniae recovered from symptomatic patients were detected on MNYC medium within 1 to 5 days of incubation, whereas 5 to 7 days of incubation were required before mycoplasmal growth was detected on PPLO agar. Over 86% of these mycoplasma isolates were detected on MNYC medium within 3 days of incubation and before the detection of any mycoplasmal growth on PPLO agar. A similar pattern of recovery times was observed for mycoplasmas isolated from asymptomatic patients. The results of this study have shown that MNYC medium is better than PPLO agar in supporting the rapid growth of M. pneumoniae from clinical specimens after 72-h blind subculture in PPLO glucose broth.