Making an accurate diagnosis of anterior mediastinal lesions: a proposal for a new diagnostic algorithm from the BTOG Thymic Malignancies Special Interest Group.

Due to the rising demand in cross-sectional thoracic imaging, anterior mediastinal lesions are being identified with increasing frequency. Following iterative and multidisciplinary discussions, the BTOG Thymic Malignancies Special Interest Group have developed an algorithm to standardise the diagnostic approach for these relatively uncommon but important conditions which span from benign (thymic remnant, thymic hyperplasia and thymic cysts) to suspected localised thymomas to suspected more aggressive malignancy (thymic carcinoma, lymphoma and germ cell tumours). For each condition, we provide a brief description, an overview of the key radiological findings and a description of the proposed algorithm including the rationale behind the recommendations. We also highlight the role of magnetic resonance (MR) imaging for the characterisation of anterior mediastinal masses in specific indications when the necessary local resources and expertise exist. In addition, we hope this provides the rationale for service development in MR of the anterior mediastinum where current resource and expertise requires development. Through this standardised pathway, we hope to drive improvements in patient care by rationalising surveillance schedules, avoiding unnecessary resections of benign entities with their associated morbidity and optimising the diagnostic work-up prior to the appropriate treatment of anterior mediastinal malignancies.

Prevalence and severity of vitamin D deficiency in patients with diabetic foot infection.

The aim of the present research was to study the prevalence and severity of vitamin D deficiency in patients with diabetic foot infection. Patients were enrolled in two groups: diabetic patients with foot infection (n 125) as cases and diabetic patients without the infection as controls (n 164). Serum 25-hydroxyvitamin D (25(OH)D) was measured by RIA. Data were presented as means and standard deviations unless otherwise indicated and were analysed by SPSS. Results revealed that 25(OH)D (nmol/l) was significantly lower (40·25 (sd 38·35) v. 50·75 (sd 33·00); P < 0·001) in cases than in controls. Vitamin D inadequacy (25(OH)D < 75 nmol/l) was equally common in cases and controls (OR 1·45, 95 % CI 0·8, 3·0; P = 0·32), but cases had a greater risk of vitamin D deficiency (25(OH)D < 50 nmol/l) than controls (OR 1·8, 95 % CI 1·1, 3·0; P = 0·02). Risk of severe vitamin D deficiency (25(OH)D < 25 nmol/l) was significantly higher in cases than in controls (OR 4·0, 95 % CI 2·4, 6·9; P < 0·0001). Age, duration of diabetes and HbA1c were significantly higher in cases than in controls and therefore adjusted to nullify the effect of these variables, if any, on study outcome. The study concluded that vitamin D deficiency was more prevalent and severe in patients with diabetic foot infection. This study opens up the issue of recognising severe vitamin D deficiency (< 25 nmol/l) as a possible risk factor for diabetic foot infections and the need for vitamin D supplementation in such patients for a better clinical outcome. This could be substantiated by similar data from future studies.

Predictors of Early Neurological Deterioration Following Intravenous Thrombolysis: Difference between Risk Factors for Ischemic and Hemorrhagic Worsening.

Background: Prevention of early neurological deterioration (END) is becoming an important therapeutic target in acute ischemic stroke management. The aim of the study is to ascertain the causes and predictors of early neurological deterioration following thrombolysis and determine the predictive value of IScore. Methods: In this single center prospective study, we analyzed clinical, imaging and outcome data in 168 patients thrombolyzed intravenously ≤4.5 hours from onset of stroke. Early neurological deterioration was defined as worsening ≥2 points in the NIHSS score at 24 hours. Results: END occurred in 34 patients (20%) and caused significantly worse short term outcome. Ischemic END (ENDi) (n = 23) was twice as common as symptomatic hemorrhage (ENDh) (n = 11). Ischemia progression (n = 15) was the most common cause. Early malignant edema was another major cause. On multivariate analysis, significant predictors (p <.05) were proximal artery occlusion [all END (p <.001), ENDi and ENDh], previous ischemic insults (all END) and raised diastolic blood pressure (ENDh). ENDi was more common in those with carotid artery occlusion, large vessel disease and previous ischemic insults. ENDh was more common in those with raised diastolic blood pressure and NIHSS-ASPECTS mismatch. For patients with NIHSS <14, IScore >105 and for NIHSS ≥14, IScore >175 was associated with higher risk of END. Conclusion: END occurs in one fifth of patients after intravenous thrombolysis; ENDi outnumbers ENDh. Proximal artery occlusion is a major predictor for END. Potentially modifiable risk factors include admission hyperglycemia and elevated blood pressures. Distinct factors characterize ENDh and ENDi and can guide prevention and management strategies. IScore identifies patients at risk for END.

Safety and tolerability of cladribine tablets in multiple sclerosis: the CLARITY (CLAdRIbine Tablets treating multiple sclerosis orallY) study.

BACKGROUND: Cladribine is a synthetic deoxyadenosine analogue in development as an oral multiple sclerosis (MS) therapy. OBJECTIVE: To report in detail the safety findings from the 96-week, phase III, double-blind CLARITY study, which evaluated treatment with cladribine tablets in relapsing-remitting MS. METHODS: A total of 1,326 patients were randomized 1:1:1 to two short-course regimens of cladribine tablets (3.5 or 5.25 mg/kg cumulative dose over 96 weeks) or placebo. Safety assessments included monitoring for adverse events (AEs), routine physical and neurologic examinations and frequent laboratory parameter assessments. RESULTS: Of the randomized patients, 88.6% completed treatment with cladribine tablets versus 86.3% with placebo. Lymphopenia was the most commonly reported AE in patients treated with cladribine tablets and was anticipated based on the mechanism of action. The incidence of infections was 48.3% with cladribine tablets and 42.5% with placebo, with 99.1% and 99.0% rated mild-to-moderate by investigators. Herpes zoster infections developed in 20 (2.3%) cladribine-treated patients; all cases were dermatomal. There were no herpes zoster infections in the placebo group. Nine (1.0%) patients experienced events related to uterine leiomyomas in the cladribine tablets groups versus one (0.2%) with placebo. Three isolated cases of malignancy were reported in cladribine-treated patients during the study; a fourth was reported during post-study surveillance. A pre-malignant cervical carcinoma in situ was also reported. The incidence of malignancies during the study did not exceed the expected rate in a population standardized for country, gender and age. CONCLUSION: The safety and tolerability profile observed in the CLARITY study together with the reported efficacy support the potential for cladribine tablets as an MS therapy.

Hypnic Headache: A Rare Primary Headache Syndrome in an Indian Population with a Mini Review of Literature.

CONTEXT: Hypnic headache (HH) is a rare primary headache syndrome first described by Raskin in 1988. AIM: To describe the occurrence of HH in Indian patients and compare its clinicoepidemiological features to those published in the literature and attempt to trace some of the evolving concepts regarding its etiology and clinical features since it was first described. MATERIALS AND METHODS: Patients attending the neurology outpatient department of a tertiary referral teaching hospital from 01-05-2011 to 30-04-2016 who were identified to have HH as per ICHD 3 beta criteria were included in the study. A meticulous history of the headache and comorbidities, clinical examination, Epworth Sleepiness Scale, blood counts, blood biochemistry, magnetic resonance imaging (MRI) scans of the brain and polysomnography (in selected patients) were done and the results were compared to selected international literature. RESULTS: A total of 11 patients with HH were identified during the study period, of which 8 (72.72%) were males and 3 (27.27%) were females. The age of the patients varied from a minimum of 53 years to a maximum of 78 years (Mean: 63.36, SD: 8.09). The frequency of attacks per month ranged from 5 to 46(Mean: 20.36, SD: 11.67). The duration of each headache episode ranged from a minimum of 30 minutes to a maximum of 4 hours (Mean: 1.93, SD: 1.23). The occurrence of the headaches was maximum during the time periods of 0.00-2.00am and 2.00-4.00am (38% and 36%, respectively). The pain was dull in a majority of patients, 7 (63.63%). Trigeminal autonomic features such as lacrimation, ptosis, or rhinorrhea were not recorded from our cohort. Motor activity was noted in 7 (63.63%) cases. Two (18.18%) patients had associated migraine headaches whereas 3 (27.27%) had associated tension-type headaches. None of the patients in our series had chronic obstructive pulmonary disease. Four (36.36%) patients had systemic hypertension and 1 patient (9.09%) had diabetes mellitus. Two (18.18%) patients had symptoms of obstructive sleep apnea syndrome. Three (27.27%) patients had symptoms of excessive daytime sleepiness according to the Epworth Sleepiness Scale. Blood examinations and MRI were normal in all patients, except for the findings of a few lacunar infarcts and nonspecific T2 weighted hyperintensities in 3 patients (27.27%). CONCLUSION: Our study proves the existence of the newly described primary headache syndrome called HH in the Indian population. On comparing our results with the international literature, the similarities are much greater than the differences. MRI voxel-based morphometry to demonstrate the loss of gray matter in the posterior hypothalamus may prove to be a reliable test to diagnose primary HH in the future.

Migraine and Mood Disorders: Prevalence, Clinical Correlations and Disability.

INTRODUCTION: Both migraine and mood disorders are prevalent disorders with many studies demonstrating that they are comorbid with each other with increased migraine-related disability in such patients. AIM: The aim of the study is to test the hypothesis that mood disorders are comorbid with migraine with increased disability and to identify any clinical features in migraineurs which may be associated with mood disorders. MATERIALS AND METHODS: Patients presenting with complaints of headache to the Neurology Outpatient Department of a Tertiary CARE Hospital from August 01, 2016 to February 28, 2017, were subjected to International Classification of Headache Disorder 3 beta criteria to satisfy a diagnosis of migraine and were assessed in detail as to headache characteristics. Mood disorders were assessed by Hospital Anxiety and Depression Scale and migraine-related disability was assessed by Migraine Disability Assessment Questionnaire. Patients with serious medical complaints, known previous psychiatric disease, other types of headaches and recent prophylactic drug intake were carefully excluded. RESULTS: A total of 133 patients were studied. The duration and frequency of migraine headaches were found to correlate with the presence of mood disorders and the migraine-related disability in patients with comorbid mood disorders was significantly higher. Factors such as total duration of migraine, aura, vomiting, phono, and photophobia were not found to be statistically correlated with mood disorders. CONCLUSIONS: Rates of depression and anxiety in migraine vary widely in various studies due to variations in study criteria, population characteristics and various scales used. We found a prevalence of 16.54% of anxiety and 9.02% of depression in migraineurs, a rate comparable to or less than many studies in international literature and a significantly increased disability in individuals with comorbid mood disorders and migraine. Routinely including questionnaires such as HAD in screening patients with migraine to rule out comorbid mood disorders may be warranted. Because we have carefully excluded all other primary (especially tension and medication overuse headaches) and secondary headaches and selected prophylactic drug naïve patients, we contend that this study provides a clear clinical profile of migraineurs with mood disorders.

Clinical Features and Psychiatric Comorbidity of Epicrania Fugax.

BACKGROUND: Epicrania fugax (EF) is a rare newly described primary headache characterized by paroxysms of unilateral pain radiating across one hemicranium. AIM: We aimed to describe 10 new cases of EF and assess the psychiatric comorbidity. MATERIALS AND METHODS: Cases of EF were identified from patients attending the neurology outpatient department of a tertiary level referral and teaching hospital by the first author during a period extending from January 1, 2015 to April 31, 2017. Case ascertainment was done as per ICHD 3 beta criteria from among patients presenting with complaints of headache after detailed history and clinical examination. Clinical and demographic features were noted and patients were subjected to Mini Neuropsychiatric Interview to screen for psychiatric comorbidity followed by Becks Anxiety/Depression Inventory. RESULTS: A total of 10 subjects were obtained during the study period, 4 males, and 6 females. Mean age of subjects was 45.3 years (standard deviation-10). Seventy percent had anteroposterior, and 30% had posteroanterior radiation of pain. The most common character of pain was stabbing (50%) followed by electrical (40%) and pressing (10%). None of the subjects had autonomic symptoms or focal symptoms in the scalp while 30% subjects had hyperesthesia in the affected area of the scalp. Six subjects (60%) patients had episodic course while 40% had chronic course. Sixty percent had comorbid anxiety while one (10%) had comorbid depression. A significant relation was obtained between duration of disease and occurrence of anxiety as well as Becks Anxiety Inventory scores while there was no correlation with attack duration. There was also a nonsignificant correlation between visual analog score and occurrence of anxiety symptoms. CONCLUSIONS: Our study conclusively proves the existence of EF as a rare, distinct primary headache syndrome in our study population. It has a significant psychiatric comorbidity consisting of 60% of generalized anxiety disorder, 10% of panic attacks, and 10% of depression.

Cerebral cortical lesions in multiple sclerosis detected by MR imaging at 8 Tesla.

BACKGROUND AND PURPOSE: Conventional imaging of ex-vivo brain at 1.5T in multiple sclerosis (MS) detects only a small fraction of the gray matter cerebral cortical lesions that can be detected by pathology. Our purpose was to examine if imaging at 8T can detect plaques in cortical gray matter (CGM) not evident at 1.5T. METHODS: An ex-vivo brain obtained at autopsy from a patient with MS was formalin fixed and 1 cm coronal slices were examined using MR imaging at 8T. RESULTS: Numerous cerebral cortical lesions not evident at 1.5T were seen at 8T. Lesions were easily identified using gradient-echo and spin-echo (SE) as well as diffusion images. MR imaging at 8T identified many of the types of plaques previously evident only by pathology. The magnitude of the cortical involvement in this 1 patient was severe. Lesions in the gray matter readily visible by high-field MR imaging were sometimes barely visible by pathology. MR imaging at 8T often facilitated the detection of such plaques by pathology. CONCLUSION: This study establishes the utility of high-field imaging at 8T in the delineation of plaques in the cerebral CGM in MS.

Nummular headache: Clinico-epidemiological features in South Indian population.

CONTEXT: Nummular headache (NH) is a primary disorder characterized by head pain exclusively felt in a small-rounded area typically 2-6 cm in diameter. AIMS: The aim of this review is to study the clinical and epidemiological features of NH in a patient population of South India and to compare this with that of described in the international literature. SETTINGS AND DESIGN: A prospective, observational study conducted in a tertiary care center. MATERIALS AND METHODS: Patients attending the medicine and neurology outpatient departments of a tertiary referral hospital in South India diagnosed to have NH as per the International Classification of Headache Disorders 3 beta (2013) criteria were studied over 30 months. All of the patients had a normal neurological examination. Neuroimaging findings were normal, except in one patient. RESULTS: A total of 19 females and 10 males were studied. The mean age of onset was 47.62 years (range 36-60). The duration of headache varied from a minimum of 3 months to a maximum of 5 years, with a mean of 24.17 months. The site of headache was predominantly in the parietal area 15 (51.72%), followed by the occipital area 7 (24.13%). The mean diameter of the affected area was 3.23 cm. The intensity of the headache proved to be mild to moderate with a mean visual analog scale score of 5.03. The quality of pain was mainly felt as burning dysesthesia 12 (41.38%). In the majority of patients, i.e. 21 (72.41%), pain was chronic and continuous. None of the patients had any significant trophic change even though paresthesias, dysesthesias, and allodynia were reported by a significant minority of patients, i.e. 9 (31.03%). Only one (3.45%) patient gave a history of head injury. Ten (34.48%) out of 29 patients had other types of concurrent headaches; the majority of which proved to be migrainous, i.e. 7 (24.14%), 2 patients (6.89%) with tension headache, and 1 patient (3.45%) with trigeminal neuralgia. CONCLUSION: Our study proves the existence of the newly described primary headache syndrome called NH in South Indian population. In comparing our results with the international literature, the number of similarities is much greater than the differences. The etiology of pain in our series appeared to be primarily peripheral with a role for central pain sensitization in some cases due to a variety of concurrent central causes of head pain.

Revised Recommendations of the Consortium of MS Centers Task Force for a Standardized MRI Protocol and Clinical Guidelines for the Diagnosis and Follow-Up of Multiple Sclerosis.

An international group of neurologists and radiologists developed revised guidelines for standardized brain and spinal cord MR imaging for the diagnosis and follow-up of MS. A brain MR imaging with gadolinium is recommended for the diagnosis of MS. A spinal cord MR imaging is recommended if the brain MR imaging is nondiagnostic or if the presenting symptoms are at the level of the spinal cord. A follow-up brain MR imaging with gadolinium is recommended to demonstrate dissemination in time and ongoing clinically silent disease activity while on treatment, to evaluate unexpected clinical worsening, to re-assess the original diagnosis, and as a new baseline before starting or modifying therapy. A routine brain MR imaging should be considered every 6 months to 2 years for all patients with relapsing MS. The brain MR imaging protocol includes 3D T1-weighted, 3D T2-FLAIR, 3D T2-weighted, post-single-dose gadolinium-enhanced T1-weighted sequences, and a DWI sequence. The progressive multifocal leukoencephalopathy surveillance protocol includes FLAIR and DWI sequences only. The spinal cord MR imaging protocol includes sagittal T1-weighted and proton attenuation, STIR or phase-sensitive inversion recovery, axial T2- or T2*-weighted imaging through suspicious lesions, and, in some cases, postcontrast gadolinium-enhanced T1-weighted imaging. The clinical question being addressed should be provided in the requisition for the MR imaging. The radiology report should be descriptive, with results referenced to previous studies. MR imaging studies should be permanently retained and available. The current revision incorporates new clinical information and imaging techniques that have become more available.

Central nervous system involvement in the eosinophilia-myalgia syndrome.

A patient with eosinophilia-myalgia syndrome developed progressive central nervosa system involvement that did not improve despite discontinuation of L-tryptophan therapy. Neurologic impairment was manifested initially by spastic monoparesis, which was improved by treatment with methyl-prednisolone and hydroxyurea. Recurrence of weakness was accompanied by gait ataxia, dysphagia, and complaints of a gradual decline in memory and concentration. Neuropsychological testing identified a broad pattern of cognitive deficits suggestive of a subcortical dementia, and magnetic resonance imaging demonstrated multiple high-signal lesions in the white matter. Cognitive deficits appear to be underrecognized in patients with the eosinophilia-myalgia syndrome. The response of our patient's initial symptoms to corticosteroid therapy suggests a possible role for autoimmune mechanisms in the pathogenesis of central nervous system involvement in the eosinophilia-myalgia syndrome. Neuropsychological evaluation should be performed in patients with cognitive complaints to delineate the full spectrum of central nervous system impairment associated with the eosinophilia-myalgia syndrome.

The relationship of complement-mediated microvasculopathy to the histologic features and clinical duration of disease in dermatomyositis.

Accumulating evidence indicates that a complement-mediated microvasculopathy may play a pathogenic role in dermatomyositis. In a previous study, we demonstrated neoantigens of the C5b-9 complement membrane attack complex in the muscle microvasculature of childhood and adult cases of dermatomyositis. To further characterize the relationship between the vascular complement deposits and histologic changes, quantitative histopathologic analyses were performed on 39 dermatomyositis biopsy specimens (26 adult, 13 children). There was a significant correlation between the percentage of fascicles with fibers having focal myofibrillar loss, a change seen early in the evolution of ischemic muscle fiber damage, and the percentage of fascicles having capillary deposits of membrane attack complex. Conversely, in biopsy specimens with a higher percentage of fascicles with perifascicular atrophy, membrane attack complex deposits were significantly less common. A fascicle-by-fascicle analysis supported these observations. Patients whose biopsy specimens were negative for microvascular membrane attack complex had clinical weakness for a significantly longer time than those patients with vascular complement deposits. These data support the hypothesis that the complement-mediated vasculopathy is a primary immunopathogenic event in the evolution of muscle lesions in dermatomyositis.

Screening for cognitive dysfunction in multiple sclerosis.

BACKGROUND: With the use of comprehensive neuro-psychological assessments, a substantial proportion of patients with multiple sclerosis have been found to have substantial cognitive impairment. Although data generated from comprehensive examinations are useful in making recommendations for treatment interventions and compensatory strategies, the cost of such assessments prohibits their use with all patients. OBJECTIVE: To develop a screening battery to detect cognitive impairment in patients with multiple sclerosis that is sensitive, specific, brief, and cost-effective, and could identify patients who might benefit from a more comprehensive neuropsychological examination. DESIGN: On the basis of a comprehensive neuropsychological assessment battery, the presence of significant cognitive impairment was determined in patients with multiple sclerosis. The screening battery consisted of a subset of tests from the comprehensive battery. Performance on the screening battery was then used to predict presence of cognitive impairment on the comprehensive battery in validation and cross-validation samples. Severity of impairment on the screening battery was also regressed on ratings of functional impairment derived from the Expanded Disability Status Scale. RESULTS: In the validation sample, the screening battery had 100% sensitivity, 80% specificity, and 88.1% overall diagnostic accuracy. In the cross-validation sample, the screening battery had 100% sensitivity, 81.8% specificity, and an overall diagnostic accuracy rate of 90.7%. chi 2 tests showed that the accuracy of the screening battery was significantly better than chance in both samples. Performance on the screening battery also predicted the level of disability ratings on the Expanded Disability Status Scale and functional systems scales. CONCLUSIONS: The screening battery had a high degree of sensitivity, specificity, and diagnostic accuracy, while maintaining a brief administration time and high cost-effectiveness. The screening battery also predicted higher levels of disability and functional impairment as assessed by the Expanded Disability Status Scale, thereby enhancing its clinical utility. Despite its advantages, the findings do not suggest that the screening battery may be an effective substitute for a more detailed examination.

Magnetic resonance imaging correlates of dementia in multiple sclerosis.

Thirty-two patients with clinically definite multiple sclerosis were evaluated with neuropsychological procedures and magnetic resonance imaging (MRI). Neuropsychological evaluation included assessment of language, memory, cognition, visuospatial skills, and depression. Significant impairment in any three areas, compatible with diagnosis of a dementia syndrome, was observed in 28% of these patients, and lesser or no cognitive impairment characterized the remaining patients. Magnetic resonance imaging was used to evaluate the number and distribution of lesions as well as the presence of cerebral atrophy and atrophy of specific anatomic structures such as the corpus callosum. Results suggest that neither the number of lesions, the distribution of lesions, nor the extent of generalized cerebral atrophy was significantly greater in demented compared with non-demented patients. The primary finding was that atrophy of the corpus callosum was significantly more extensive on MRI scans in demented patients. Although the callosum itself may not be implicated directly in the pathogenesis of dementia, the presence of callosal atrophy on MRI scans should alert the physician to the possible occurrence of dementia in patients with multiple sclerosis.

Immunosuppressive treatment of motor neuron syndromes. Attempts to distinguish a treatable disorder.

OBJECTIVE: To determine if response to immunosuppressive treatment in motor neuron syndromes could be predicted on the basis of clinical features, anti-GM1 antibodies, or conduction block. DESIGN: Prospective, uncontrolled, treatment trial using prednisone for 4 months followed by intravenous cyclophosphamide (3 g/m2) continued orally for 6 months. SETTING: All patients were referred to university hospital medical centers. PATIENTS: Sixty-five patients with motor neuron syndromes were treated with prednisone; 11 patients had elevated GM1 antibody titers, and 11 patients had conduction block. Forty-five patients received cyclophosphamide, eight of whom had elevated GM1 antibodies and 10 had conduction block. RESULTS: One patient responded to prednisone, and five patients responded to cyclophosphamide treatment. Only patients with a lower motor neuron syndrome and conduction block improved with either treatment. Response to treatment did not correlate with GM1 antibodies. CONCLUSIONS: GM1 antibodies did not serve as a marker for improvement in patients with motor neuron syndrome treated with immunosuppressive drugs. Patients with amyotrophic lateral sclerosis failed to improve irrespective of laboratory findings.

Subacute sclerosing panencephalitis after passive immunization and natural measles infection: role of antibody in persistence of measles virus.

Subacute sclerosing panencephalitis (SSPE) developed in a patient in whom natural measles infection was anteceded by immunization with measles immune serum globulin (ISG). This observation prompted experimental studies of the role of antibody in viral persistence. When Balb/c mice were infected with the hamster neurotropic measles virus, acute encephalopathy was fatal in 80% of the animals. When measles antibody was administered 3 days after virus inoculation, the acute disease was abolished and subacute encephalitis had a 30% mortality. The subacute disease was characterized by the presence of neuronal viral antigen, meningitis, and encephalitis. Induction of viral persistence was therefore a consequence of antibody transfer during viral infection. Caution is advised in human prophylaxis with immune globulin.

Mononuclear cell analysis of muscle biopsies in prednisone-treated and untreated Duchenne muscular dystrophy. CIDD Study Group.

A recent double-blind, placebo-controlled trial has shown that prednisone improves strength in patients with Duchenne muscular dystrophy. To determine whether immunosuppressant effects were important in mediating this improvement, we performed immunohistochemical analyses on muscle biopsies obtained at the conclusion of the trial. We studied 33 patients: 12 from the placebo group, nine from the low-dose prednisone group (0.75 mg/kg/d), and 12 from the high-dose group (1.5 mg/kg/d). There was a significant difference in total T cells (CD2+) between the placebo group and both treatment groups. Similarly, the number of CD8+ cytotoxic/suppressor T cells was significantly decreased in both treated groups compared with placebo. The number of muscle fibers focally invaded by lymphocytes was also significantly decreased in the two treated groups compared with controls. There were no differences between the low- and high-dose groups. The numbers of B cells, natural killer cells, CD4+ cells, macrophages, and necrotic muscle fibers were not significantly different in the treated and control groups. This study suggests that prednisone may improve strength in Duchenne muscular dystrophy through primarily immunologic mechanisms involving T lymphocytes.

Evidence for central nervous system demyelination in chronic inflammatory demyelinating polyradiculoneuropathy.

It is unclear whether sporadic reports of concurrent multiple sclerosis (MS) and chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) represent coincidence or whether these two demyelinating disorders are pathogenically related. We utilized the sensitivity of magnetic resonance imaging (MRI) in detecting central nervous system (CNS) lesions to investigate 16 patients with CIDP. Six of the 16 had periventricular, subcortical, and brainstem white matter lesions indistinguishable from those seen in MS. Three of these patients had definite clinical and laboratory evidence of MS; three others with abnormal MRIs had no findings indicative of CNS disease. Previous reports have indicated that a significant number of MS patients have peripheral nerve demyelination. Our study suggests that many CIDP patients have concurrent CNS demyelination. Taken together, these observations support the existence of a central-peripheral inflammatory demyelinating syndrome. Whether this combined demyelinating syndrome lies on a spectrum between MS and CIDP or is a separate pathogenic entity will require further investigation.

Dystrophin expression and somatic reversion in prednisone-treated and untreated Duchenne dystrophy. CIDD Study Group.

The mechanism by which prednisone improves muscle strength and function in Duchenne muscular dystrophy (DMD) is unknown. We addressed the possibility that clinical improvement was related to prednisone-induced alterations in skeletal muscle dystrophin. We performed muscle biopsies on patients at the conclusion of a randomized, double-blind, 6-month trial of prednisone and analyzed dystrophin content using Western blots and antibody staining of tissue sections. These studies demonstrated no significant differences in dystrophin content between treatment (prednisone 1.5 mg/kg/d, n = 12; prednisone 0.75 mg/kg/d, n = 9) and placebo (n = 12) groups. Of interest, however, was the presence of varying numbers of dystrophin-positive fibers (revertants) occurring individually or in clusters in antibody-stained tissue sections of more than one-half of the Duchenne patients. Mutation analysis revealed that revertants occurred in DMD patients with identifiable deletions half of the Duchenne patients. Mutation analysis revealed that revertants occurred in DMD patients with identifiable deletions or duplications, and in nondeletion patients. Prednisone treatment did not influence the prevalence of revertants. Revertants are most likely due to a second-site mutation occurring in a somatic cell allowing for restoration of the translational reading frame of the dystrophin transcript.

Mononuclear cell analysis of muscle biopsies in prednisone- and azathioprine-treated Duchenne muscular dystrophy.

Prednisone improves strength and function in patients with Duchenne dystrophy. Although the mechanism of this effect is uncertain, prior studies suggested that the benefit might result from immunosuppressive effects on T lymphocytes invading muscle. A recent randomized, double-blind, controlled trial of prednisone and azathioprine demonstrated that azathioprine had no effect in Duchenne dystrophy, raising questions about the role of immunosuppression in mediating clinical improvement. The goal of this current study was to compare the effects of prednisone and azathioprine on mononuclear infiltrates from biopsies performed at the end of the controlled clinical trial (reported separately in the article by Griggs et al on page 520). We studied 14 patients from the prednisone group (0.75 mg/kg/d), 10 from the combination therapy group (prednisone 0.3 mg/kg/d and azathioprine 2.5 mg/kg/d), and 13 from the azathioprine group (2.5 mg/kg/d), and used monoclonal antibodies for cell typing. There were no significant differences between the groups for total T cells, T-cell subsets, B cells, natural killer cells, total mononuclear cells, necrotic muscle fibers, or fibers focally invaded by mononuclear cells. These data indicate that azathioprine decreases mononuclear subsets infiltrating muscle to a similar degree as does prednisone, although azathioprine-treated patients do not show a clinical improvement. This implies that immunosuppressive actions on cellular infiltrates in muscle are probably not the primary mechanism of prednisone-induced clinical improvement.