Recovery of cognitive function after relapse in multiple sclerosis.

BACKGROUND: Cognitive impairment is common in multiple sclerosis (MS) but its manifestation as acute disease activity is underappreciated. OBJECTIVE: The aim of this study is to examine recovery after MS relapse on multiple tests of cognitive and motor function and explore correlates of change with Expanded Disability Status Scale (EDSS), magnetic resonance imaging (MRI), and cognitive reserve. METHODS: Fifty relapsing group (RG) and matched stable participants were examined at baseline, during relapse, and at 3-month follow-up. Tests of cognitive processing speed (Symbol Digit Modalities Test (SDMT)) and consensus opinion measures of memory, ambulation, and manual dexterity were administered. All RG patients were treated with a 5-day course of Acthar Gel (5 mL/80 IU). RESULTS: In RG patients, SDMT declined from 55.2 to 44.6 at relapse and recovered to 51.7, a slope differing from stable controls (p = 0.001). A statistical trend (p = 0.07) for the same effect was observed for verbal memory and was significant for ambulation (p = 0.03). The Cerebral Function Score from the EDSS also changed in the RG and recovered incompletely relative to controls (p = 0.006). CONCLUSION: These results replicate earlier reports of cognitive worsening during relapse in MS. Clinically meaningful improvements followed relapse on SDMT and ambulation. Cognitive decline during relapse can be appreciated on neurological exam but not patient-reported outcomes.

Quantifying cognition and fatigue to enhance the sensitivity of the EDSS during relapses.

BACKGROUND: Cognition is affected by relapses in persons with multiple sclerosis (PwMS), yet the Expanded Disability Status Scale (EDSS) does not readily detect cognitive changes. OBJECTIVE: The objective of this study is to improve the detection of cognitive decline during relapses, by incorporating the Symbol Digit Modalities Test (SDMT) into the cerebral Functional System Score (CFSS) of the EDSS. METHODS: This prospective study recruited PwMS from three dedicated MS centers. All subjects had EDSS, SDMT, and Fatigue Severity Scale (FSS) administered. Subjects experiencing a relapse were assigned to the relapse group (RG). Matched controls from the larger cohort were assigned to the stable group (SG). RG and SG subjects underwent the same evaluation at relapse and 3 months later. Our main outcomes were a modified CFSS (m-CFSS) and modified EDSS (m-EDSS), incorporating SDMT and FSS, accounting for cognitive performance and fatigue rating, during relapse. RESULTS: The full cohort included 592 subjects; 80 qualified for RG and 72 were matched to the SG. The m-CFSS was significantly higher than CFSS at baseline (median = 2 vs. median = 0, p < 0.001) and relapse (median = 2 vs. median = 1, p < 0.001). The m-EDSS was higher than EDSS (median 3.0 vs. 2.5, p = 0.02) at relapse, where 35 RG subjects (43.8%) had higher m-EDSS than EDSS at relapse. CONCLUSION: This study demonstrates that incorporating the SDMT and FSS improves the accuracy of the EDSS, by accounting for cognitive changes, during relapse activity.

Necessity of technicians for computerized neuropsychological assessment devices in multiple sclerosis.

OBJECTIVE: Determine the influence of technician supervision on computer-administered cognitive tests in multiple sclerosis (MS). METHODS: Eighty MS patients underwent assessment using the CogState Brief Battery (CSBB) and the Cleveland Clinic Cognitive Battery (C3B). Each was administered twice, once with a technician guiding assessment, and once with technician-absent. Twenty-eight healthy controls were also evaluated. RESULTS: The influence of technician guidance was not statistically significant for group means on either test. For CSBB, administration problems were more common in the technician-absent condition. CONCLUSION: In this MS sample, reliable and valid test results were obtained from computer-assisted cognitive testing without technician guidance.

Preserved network functional connectivity underlies cognitive reserve in multiple sclerosis.

Cognitive reserve is one's mental resilience or resistance to the effects of structural brain damage. Reserve effects are well established in people with multiple sclerosis (PwMS) and Alzheimer's disease, but the neural basis of this phenomenon is unclear. We aimed to investigate whether preservation of functional connectivity explains cognitive reserve. Seventy-four PwMS and 29 HCs underwent neuropsychological assessment and 3 T MRI. Structural damage measures included gray matter (GM) atrophy and network white matter (WM) tract disruption between pairs of GM regions. Resting-state functional connectivity was also assessed. PwMS exhibited significantly impaired cognitive processing speed (t = 2.14, p = .037) and visual/spatial memory (t = 2.72, p = .008), and had significantly greater variance in functional connectivity relative to HCs within relevant networks (p < .001, p < .001, p = .016). Higher premorbid verbal intelligence, a proxy for cognitive reserve, predicted relative preservation of functional connectivity despite accumulation of GM atrophy (standardized-ß = .301, p = .021). Furthermore, preservation of functional connectivity attenuated the impact of structural network WM tract disruption on cognition (ß = -.513, p = .001, for cognitive processing speed; ß = -.209, p = .066, for visual/spatial memory). The data suggests that preserved functional connectivity explains cognitive reserve in PwMS, helping to maintain cognitive capacity despite structural damage.

Response heterogeneity to home-based restorative cognitive rehabilitation in multiple sclerosis: An exploratory study.

BACKGROUND: Growing evidence supports the efficacy of restorative cognitive training in people with multiple sclerosis (PwMS), but the effects vary across individuals. Differences in treatment efficacy may be related to baseline individual differences. We investigated clinical characteristics and MRI variables to predict response to a previously validated approach to home-based restorative cognitive training. METHODS: In a single-arm repeated measures study, 51 PwMS completed a 12-week at-home restorative cognitive training program called BrainHQ, shown to be effective in a placebo-controlled clinical trial. Baseline demographic, clinical, neuropsychological, and brain MRI factors were captured and the effects of treatment were quantified with Symbol Digit Modalities Test (SDMT). Also measured were indices of treatment compliance. Regression modeling was employed to identify the factors associated with greatest SDMT improvement. RESULTS: As a group, patients improved significantly after training: mean SDMT improving from 49.6 ±â€¯14.7 to 52.6 ±â€¯15.6 (t = 3.91, p<0.001). Greater SDMT improvement correlated positively with treatment exposure (r = 0.38, p = 0.007). Increased post-rehabilitation improvement on SDMT was predicted by baseline relapsing-remitting course (ß=-0.34, p = 0.017), higher trait Conscientiousness-Orderliness (ß=0.29, p = 0.040), and higher baseline gray matter volume (GMV; ß=0.31, p = 0.030). CONCLUSION: The study was designed to explore the variables that predict favorable outcome in a home-based application of a validated restorative cognitive training program. We find good outcomes are most likely in patients with higher trait Conscientiousness-Orderliness, and relapsing-remitting course. The same was found for individuals with higher GMV. Future work in larger cohorts is needed to support these findings and to investigate the unique needs of individuals according to baseline factors.

Management of Massively Enlarged Multiple Hydatid Cysts in the Liver of a Pediatric Patient.

Multiple hydatid cysts in the liver are a very rare occurrence in childhood. We present a similar case in a nine-year-old girl, a resident in a rural community, who presented with two hydatid cysts in her liver. The cysts were operated upon by a pediatric surgeon. The laboratory findings of this patient showed peripheral blood eosinophilia, elevated white blood cells, and liver enzymes. The serology was positive. The ultrasonography showed cystic masses in the liver, and the diagnosis of hydatid cysts was eventually confirmed by computed tomography (CT) of the abdomen.

Marked Atrophic Changes of the Brain in a Patient with Subacute Sclerosing Panencephalitis.

Subacute Sclerosing Panencephalitis (SSPE) is a debilitating disorder associated with the measles infection in childhood. It is a very rare manifestation in children. It usually presents with measles before the age of two. We report a similar case of SSPE in a 14-year-old girl who developed this life-threatening condition in spite of receiving the measles vaccination. Despite the vaccination, the patient had suffered from measles before the age of two. This highlights the dilemma of ineffective vaccinations in developing countries. We also describe the radiologic features of SSPE in this patient, with marked atrophy seen in the occipital region following hyperintensities noticed at a relatively earlier stage.

Extensive Pyoderma Gangrenosum: A Challenging Diagnosis and Literature Review of Management.

Pyoderma gangrenosum is a very rare, non-infectious leukocytic dermatosis, which is often associated with an underlying systemic disease. It is usually diagnosed based on the apparent clinical findings and by excluding other causes of ulcerative skin diseases. Treatment modality includes the use of systemic steroids and oral steroids. Immunosuppressive agents, such as cyclosporine and mycophenolate mofetil, can also be added if it fails to respond to steroids. We report a case of pyoderma gangrenosum in an 85-year-old female who presented in the inpatient facility with rapidly enlarging necrotic, ulcerative lesions with accompanying fever. She was managed with systemic steroids to which she responded well. This led to the arrest of the initially progressive lesions with some residual scarring.

Combination Therapy for Multidrug-Resistant Klebsiella Pneumoniae Urinary Tract Infection.

Hospital-acquired multidrug-resistant (MDR) Klebsiella infection is posing a significant challenge to physicians all around the world. The spread of multiple antibiotic resistance among various members of bacteria continues to be a significant clinical threat. Antibiotic susceptibility testing is the initial step in optimizing the appropriate antibiotic therapy for infections with MDR Klebsiella. We report a case of MDR Klebsiella urinary tract infection (UTI) in a patient following a trimalleolar fracture, which was appropriately treated with a combination of amikacin and meropenem.

Breast Cancer Metastases to the Gastrointestinal Tract Presenting with Anemia and Intra-abdominal Bleed.

Signet ring adenocarcinoma of the breast with synchronous metastasis to the gastrointestinal (GI) tract is a rare occurrence, typically presenting with abdominal pain, dyspepsia, or GI bleed. We report a case of metastatic breast cancer presenting with a complaint of anemia. A further diagnostic evaluation revealed generalized lymphadenopathy, nodular thickening of the urinary bladder wall, bone lesions, and enlarged pancreas. Biopsies from the lymph nodes, pancreatic biopsy, and bladder nodule all revealed a signet cell carcinoma. An upper and lower GI endoscopy revealed multiple ulcerated gastric mucosal nodules and polypoid folds in the cecum and proximal ascending colon; the biopsies from these lesions were also positive for signet ring cell adenocarcinoma.