scholarly journals Hereditary defect of cobalamin metabolism with adolescence onset resembling multiple sclerosis: 41-year follow up in two cases

2019 ◽  
Vol 12 ◽  
pp. 175628641987211 ◽  
Author(s):  
Jeremias Motte ◽  
Janina Kneiphof ◽  
Katrin Straßburger-Krogias ◽  
Kalliopi Pitarokoili ◽  
Anna Lena Fisse ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Late Onset ◽  
Demyelinating Diseases ◽  
Clinical Severity ◽  
High Dose ◽  
Healthy Children ◽  
First Case ◽  
Initial Symptoms ◽  
Hereditary Defect

The cblC defect is the most common inborn error of cobalamin (Cbl) metabolism. Clinical severity and presentation of the cblC defect ranges from death to mild disability. Only 71 cases of late-onset cblC defect have been described in the literature. We provide the 41-year follow up of two siblings with a late-onset cblC defect, first described after initial diagnosis in 1996. While one of the siblings showed initial symptoms resembling multiple sclerosis with a good response to corticosteroids, the other sister showed only subclinical signs of the disease. The course of the first case was characterized by a severe deterioration and intensive-care therapy after respiratory failure. After diagnoses and Cbl treatment, the patient survived and showed a pronounced improvement of the symptoms. Both sisters have an active life and gave birth to healthy children. The reason for the initial improvement after corticosteroids could not be explained by the classical metabolic pathways of Cbl. Recent studies have suggested that Cbl plays an important role as a regulator of the balance between neurotrophic and neurotoxic factors in the central and peripheral nervous system (CNS and PNS). This first long-term follow up revealed that ultra-high-dose intramuscular Hydroxocobalamin (OH-Cbl) treatment can effectively protect patients from disease progression. It underlines the importance of diagnostic vigilance and laboratory work up even in cases without typical hematologic signs of Cbl deficiency. Cbl-related diseases are often a chameleon and must always be considered in the differential of demyelinating diseases of the PNS and CNS. The case supports the theory that it is not only the classical biochemical pathways that play a key role in Cbl deficiency, especially with regard to neurological symptoms.

Cerebral venous thrombosis and demyelinating diseases: report of a case in a clinically isolated syndrome suggestive of multiple sclerosis onset and review of the literature

2005 ◽  
Vol 11 (2) ◽  
pp. 242-244 ◽  
Author(s):  
Maurizia Maurelli ◽  
Roberto Bergamaschi ◽  
Elisa Candeloro ◽  
Alessandra Todeschini ◽  
Giuseppe Micieli
Keyword(s):  
Multiple Sclerosis ◽  
Venous Thrombosis ◽  
Lumbar Puncture ◽  
Cerebral Venous Thrombosis ◽  
Corticosteroid Treatment ◽  
Clinically Isolated Syndrome ◽  
Demyelinating Diseases ◽  
High Dose ◽  
First Case ◽  
Definite Multiple Sclerosis

Cerebral venous thrombosis (CVT) has been described in several cases of clinically definite multiple sclerosis (MS). In the majority of these, lumbar puncture followed by intravenous corticosteroid treatment was suspected as the cause. We report what is, to our knowledge, the first case of a patient with a multifocal clinically isolated syndrome suggestive of MS onset, who developed multiple CVT after lumbar puncture and during high-dose i.v. corticosteroid treatment. We conclude that the sequence ‘lumbar puncture followed by corticosteroid treatment’ may be a contributory risk factor for the development of CVT when associated with other risk factors.

scholarly journals Hydrocephalus presenting as idiopathic aqueductal stenosis with subsequent development of obstructive tumor: report of 2 cases demonstrating the importance of serial imaging

2017 ◽  
Vol 20 (4) ◽  
pp. 329-333 ◽  
Author(s):  
Jarod L. Roland ◽  
Richard L. Price ◽  
Ashwin A. Kamath ◽  
S. Hassan Akbari ◽  
Eric C. Leuthardt ◽  
...  
Keyword(s):  
Late Onset ◽  
Diagnostic Testing ◽  
Subsequent Development ◽  
Mass Effect ◽  
Aqueductal Stenosis ◽  
Pineal Region ◽  
Serial Imaging ◽  
Cerebrospinal Fluid Diversion ◽  
First Case

The authors describe 2 cases of triventricular hydrocephalus initially presenting as aqueductal stenosis that subsequently developed tumors of the pineal and tectal region. The first case resembled late-onset idiopathic aqueductal stenosis on serial imaging. Subsequent imaging revealed a new tumor in the pineal region causing mass effect on the midbrain. The second case presented in a more typical pattern of aqueductal stenosis during infancy. On delayed follow-up imaging, an enlarging tectal mass was discovered. In both cases hydrocephalus was successfully treated by cerebrospinal fluid diversion prior to tumor presentation. The differential diagnoses, diagnostic testing, and treatment course for these unusual cases are discussed. The importance of follow-up MRI in cases of idiopathic aqueductal stenosis is emphasized by these exemplar cases.

CONGENITAL MICROGASTRIA, A CASE REPORT WITH A 26-YEAR FOLLOW-UP

PEDIATRICS ◽  
1973 ◽  
Vol 51 (6) ◽  
pp. 1037-1041
Author(s):  
Eugene Blank ◽  
Alvin Chisolm
Keyword(s):  
Case Report ◽  
English Language ◽  
Normal Adult ◽  
Healthy Children ◽  
Adult Size ◽  
Persistent Vomiting ◽  
First Case ◽  
English Language Journal ◽  
Roentgenographic Examination

A 27-year-old woman had congenital microgastria, which was apparent in roentgenographic examination when she was 1 year of age. Despite inability to eat anything but pureed foods for the first 13 years and despite persistent vomiting during that time, she has reached normal adult size and has three healthy children. This report represents two firsts: the first case of congenital microgastria in an English language journal of pediatrics and the first with a long follow-up.

scholarly journals The Ala/Ala genotype of PPARY Pro12 Ala polymorphism is associated with late onset of multiple sclerosis

2013 ◽  
Vol 65 (2) ◽  
pp. 447-453
Author(s):  
N. Lukic ◽  
A. Stankovic ◽  
E. Dincic ◽  
M. Bundalo ◽  
Z. Krsmanovic ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Late Onset ◽  
Age At Onset ◽  
Peroxisome Proliferator ◽  
Pro12ala Polymorphism ◽  
Peroxisome Proliferator Activated Receptor ◽  
Post Hoc ◽  
Genotype And Allele Frequencies

The function of peroxisome proliferator-activated receptor ? (PPAR?) in immune regulation, as well as in antiinflammatory and anti-proliferative actions towards T lymphocytes, has been reported. A potential role of PPARs in multiple sclerosis (MS) was suggested. The aim of this study was to investigate if there is an association of PPAR?-2 Pro12Ala polymorphism with MS in 361 patients from Serbia. The genotype and allele frequencies of Pro12Ala polymorphism were not significantly different between controls and patients, or between females and males. In contrast to controls, we detected a rare Ala/Ala genotype in patients with MS. We found that there is a significant association of Ala/Ala genotype with older age at onset (ANOVA, p=0.07; LSD post-hoc, Ala/Ala vs. Pro/Ala, p=0.03, Ala/Ala vs. Pro/Pro p=0.02). It would be useful to validate our results in other populations, as well as to perform follow-up of the disease progression in regard to PPAR? genotypes.

scholarly journals P1693LONG-TERM OUTCOME OF KIDNEY TRANSPLANTATION IN PLASMA CELLS DYSCRASIAS

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Fulvia Zappulo ◽  
Gabriele Donati ◽  
Giorgia Comai ◽  
Claudia Bini ◽  
Andrea Angeletti ◽  
...  
Keyword(s):  
Kidney Transplantation ◽  
Light Chain ◽  
Graft Failure ◽  
Case Series ◽  
University Hospital ◽  
High Dose ◽  
Light Chain Deposition Disease ◽  
Light Chain Amyloidosis ◽  
First Case

Abstract Background and Aims Survival of patients with Multiple Myeloma (MM), Light Chain Amyloidosis (LCA) and Monoclonal Gammopathies of renal significance (MGRS) on chronic renal replacement therapy (RRT) is poor. The gold standand treatment of plasma cell dyscrasias (PCD) is high-dose chemotherapy followed by Autologous Stem Cell Transplantation (ASCT) which can induce complete remission and longer survival than chemotherapy alone. Kidney transplantation (KT) after ASCT could represent an option for patients with PCD and End Stage Renal Disease (ESRD). There is no evidence about the time of follow up required from MM remission and KT. Method We present a case series of 5 patients who underwent KT after ASCT and remission of MM among 2,500 transplant recipients followed at the Nephrology Dialysis and Renal Transplantation Unit of S.Orsola University Hospital from 1967 untill now. As in case of recovery from solid cancers, the feasibility of KT after MM was considered when no signs of relapse were assessed. In our cohort 3 patients were affected by Light Chain Deposition Disease (LCDD), 1 patient presented Myeloma Cast Nephropathy (MCN) and one patient Light Chain Amyloidosis (LCA). They all required RRT and underwent KT after ASCT. Results Time between ASCT and KT ranged from 3 and 11 years and clinical outcome was very different. The mean follow up period ranged from 2 to 4 years. In the first case (LCDD) KT was performed 11 years after ASCT, the graft failure occurred 6 years later because of chronic allograft nephropathy requiring RRT. In the second case (LCDD) patient received KT 3 years after ASCT. He developed Bence-Jones proteinuria requiring specific therapy with Dexametasone and Bortezomib determining progressive graft failure. In the third case (LCDD) KT was performed 4 years after ASCT and the 4 year follow up is negative for relapse of MM or ESRD. The fourth patient presented MCN and received KT 8 years after ASCT. MCN relapsed 6 years later; it caused ESRD requiring RRT. In the last patient (LCA) KT was performed 4 years after ASCT. No recurrence occurred in a 2-year follow up. Conclusion MM is the most frequent malignancy in dialytic population; the need for KT in MM remains high. ASCT improves the quality of life and offers higher survival in patients with myeloma/MGRS/amyloidosis-related ESRD. Therefore the combination of chemotherapy/ASCT and KT is pivotal to pursue renal restoring. Since high risk of recurrence larger study are required to clarify the better follow up period after MM remission and KT.

Effects of Dexamethasone (DEX) Vs Prednisone (PDN) and High-Dose Methotrexate (HD-MTX) Vs Capizzi Methotrexate/Asparaginase (C-MTX/ASNase) On Osteonecrosis (ON) Incidence in Children and Young Adults with High Risk Acute Lymphoblastic Leukemia (HR-ALL): A Report From the Children's Oncology Group (COG) Study AALL0232

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 665-665 ◽  
Author(s):  
Leonard A. Mattano ◽  
Meenakshi Devidas ◽  
Naomi Winick ◽  
Elizabeth Raetz ◽  
Stephen P. Hunger ◽  
...  
Keyword(s):  
Lymphoblastic Leukemia ◽  
Significant Risk ◽  
Pairwise Comparison ◽  
Clinical Severity ◽  
High Dose ◽  
Additional Risk ◽  
History Of ◽  
Children And Young Adults ◽  
Grade 3

Abstract Abstract 665 Improved treatment outcomes for HR-ALL are associated with a significant risk of symptomatic ON, particularly in adolescents. Causes are multifactorial, including exposure to DEX, MTX and ASNase. This was first noted on CCG-1882 (1991–1995), which showed more ON in slow early responders (SER) given 2 vs 1 interim maintenance/delayed intensification (IM/DI) phases as part of therapy that included C-MTX/ASNase during IM and continuous DEX (d1-21) during DI (Mattano, JCO 2000). Since 1996 the COG has prospectively monitored the occurrence of symptomatic ON in HR ALL trials. CCG-1961 (1996–2002) showed that alternate-week DEX (AWD) (d1-7, 15–21) during 2 DIs reduced ON compared with continuous DEX during 1 DI in rapid early responders (RER) (Mattano, Lancet Oncol 2012). AALL0232 (2003–2011) enrolled a total of 3154 HR-ALL patients (pts) 1–30 yr and included COG augmented therapy with a 2×2 randomization to DEX (10 mg/M2 d1-14) vs PDN (60 mg/M2 d1-28) during induction (IND) and HD-MTX vs escalating-dose C-MTX plus pegaspargase during IM. RER pts received 1 IM/DI, SER pts received 2 IM/DI; all initially received monthly DEX maintenance (MTC) pulses (6 mg/M2 d1-5). To limit ON, pts 13+ yr received AWD during 1 or 2 DI, while pts <13 yr received continuous DEX. Based on interim analyses, the study was amended twice to address unexpectedly high ON rates. After 10/2006 all pts 10+ yr received AWD during DI; after 6/2008 all pts 10+ yr were non-randomly assigned to PDN during IND, and pts of all ages received AWD during DI and PDN pulses in MTC. Detailed analyses of 2701 pts with reportable data (1405 with 24+ month follow-up) showed ON in 249 pts (228 10+ yr, 21 1–9 yr; 119 males, 130 females). Symptom onset was pre-MTC in 17.7%, during MTC in 77.9%, after therapy completion in 4.4%, and within 36 months from ALL diagnosis in 98.0%. The 36-month cumulative ON incidence was 13.5±1.1%, was higher for pts 10+ yr (19.6±1.6 vs 3.1±0.9%, RHR 6.7, p<0.0001), and increased with age (1–9 yr 3.1±0.9%, 10–12 yr 17.2±2.5%, 13–15 yr 21.9±2.7%, 16+ yr 21.2±3.3%, p<0.0001). For pts 10+ yr, ON incidence was higher in females (22.2±2.5 vs 17.4±2.1%, RHR 1.4, p=0.01). Among randomized RER pts 10+ yr (Table), ON incidence was higher for DEX vs PDN (RHR 1.8); for pts 1–9 yr, rates were similarly low but modestly higher for PDN (borderline significance). There was no difference between C-MTX/ASNase vs HD-MTX overall. However, for pts 10+ yr randomized to PDN, pairwise comparison showed a higher ON rate for C-MTX/ASNase (17.2±3.8 vs 10.3±2.7%, RHR=1.7, p=0.01). Comparison of ON incidences between randomized RER regimens showed significant differences in pts 1–9 yr (DC 1.5±1.4, DH 0.7±1.0, PC 5.6±2.6, PH 1.9±1.6%, p=0.04) and 10+ yr (DC 23.9±4.0, DH 24.7±3.7, PC 20.9±4.0, PH 9.8±2.7%, p=0.0004). Comparison of ON incidences for pts 10–12 yr given continuous DEX vs AWD in DI (pre- vs post-2006 amendment) confirmed a significantly lower rate with AWD (28.9±3.8 vs 10.3±3.1%, RHR 3.1, p<0.0001). Maximum patient ON clinical severity (CTCAE v3.0) reported for 210 of 249 pts: 6.7% grade 1, 63.3% grade 2, 29% grade 3, 1.0% grade 4. The most common sites were knee > hip > ankle. In conclusion, DEX is associated with a higher incidence of ON among pts 10+ yr receiving augmented therapy. Children 1–9 yr appear to tolerate DEX and PDN during IND with similar low ON rates. ON risk can be significantly reduced by using AWD during DI, and by using HD-MTX rather than C-MTX/ASNase with PDN based regimens. Studies are presently underway that include prospective MRI screening to further define the natural history of ON in HR ALL and to identify additional risk factors for this common toxicity. Randomized RER, 36-Month Incidence Rate (% ± SE) DEX PDN P 1-9 yr 1.1 ± 0.9 3.7 ± 1.5 0.05 10+ yr 24.3 ± 2.7 15.1 ± 2.4 0.0007 16+ yr 25.6 ± 6.0 13.7 ± 4.9 0.04 C-MTX HD-MTX P 1-9 yr 3.6 ± 1.4 1.6 ± 0.9 0.09 10+ yr 19.1 ± 2.4 18.3 ± 2.2 0.4 16+ yr 16.4 ± 4.7 24.0 ± 4.5 0.2 Disclosures: Mattano: Pfizer: Employed 2009–2012 Other, Equity Ownership.

Autologous Hematopoietic Stem Cell Transplantation In Neuromyelitis Optica: A Retrospective Study Of The EBMT Autoimmune Diseases Working Party In Collaboration With The University Of Sao Paulo, Ribeirao Preto, Brazil

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 2125-2125
Author(s):  
Raffaella Greco ◽  
Attilio Bondanza ◽  
Manuela Badoglio ◽  
Myriam Labopin ◽  
Maria Carolina Oliveira ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Stem Cell ◽  
Retrospective Study ◽  
Stem Cell Transplantation ◽  
Autoimmune Diseases ◽  
Working Party ◽  
High Dose ◽  
Free Survival ◽  
Disease Response

Abstract Background Neuromyelitis optica (NMO) is an inflammatory and demyelinating disorder of the central nervous system. Recently NMO has been recognized as an autoimmune astrocytopathy, distinct from multiple sclerosis and hallmarked by pathogenic anti-aquaporin 4 (AQP4) antibodies (Kim et al, Mult Scler, 2013). Currently NMO carries a poorer prognosis than multiple sclerosis (MS) and its response to various immunosuppressive treatments remains largely unsatisfactory. Use of Autologous stem cell transplantation (ASCT) has been reported worldwide as a tool for inducing prolonged restoration of self-tolerance in MS and other severe autoimmune diseases (AD), refractory to conventional treatments. In this context, NMO treatment resistant cases were considered for ASCT on a ‘Clinical Option’ basis, according to EBMT guidelines (Snowden et al, Bone Marrow Transplant, 2012). Only 2 isolated NMO cases with contradictory results (Matiello et al, Arch Neurol, 2011; Peng et al, Neurologist, 2010) and a Chinese report of 21 opticospinal multiple sclerosis patients treated by ASCT (Xu et al, Ann Hematol, 2011) are reported in the literature. Therefore, the EBMT Autoimmune Diseases Working Party (ADWP) conducted a survey to address NMO disease response following ASCT. Methods This retrospective study followed the EBMT study guidelines. All centers were invited to participate. Sixteen patients with aggressive forms of NMO refractory to standard treatments treated by ASCT between 2001 and 2011 had been reported to the EBMT registry. For each case, a specific questionnaire was sent to complete information by referring haematologist and neurologist about NMO, ASCT and outcome including disease response, relapse and progression. Results are reported as median. Results Patients (13 females and 3 males) had a median age of 37 years at transplant. Previous treatments had included high-dose steroids (12/16), immunoglobulins (5/16), iv cyclophosphamide (Cy, in 8/16), rituximab (5/16), mitoxantrone (2/16), plasma exchanges (8/16), azathioprine (5/16) and methotrexate (1/16). Median time between NMO diagnosis and transplant was 24 months. Before ASCT, the median EDSS (the Kurtzke Expanded Disability Status Scale) was of 6.5, 10/16 patients were positive for AQP4 antibodies and 11/16 had active lesions on magnetic resonance imaging (MRI). Peripheral blood stem cells mobilization, high-dose alkylating agent such as Cy (14/16) or monoclonal antibodies as Rituximab (2/16), followed by granulocyte colony stimulating factor (G-CSF), was successfully achieved in all cases (16/16). The conditioning regimen consisted of BEAM plus anti-thymocyte globulin (9/16) or Thiotepa-Cy (3/16) or Cy and anti-thymocyte globulin (4/16). Hematopoietic recovery was documented in all patients within 10 days (range 3-25) after ASCT, both for neutrophils and platelets, with a median number of 4 red blood cells and 5 platelet units transfusions. Infectious complications required specific treatment in 9 patients (6 febrile neutropenia, 5 CMV and 2 VZV reactivations, 1 aspergillosis). All patients responded initially. Relapse, necessitating further treatments, occurred in 13/16 at a median of 7 months after ASCT, presenting a median EDSS of 7 (range 3-8.5) and a worsening of MRI (11 cases). NMO progression was observed in 9/16 patients at a median of 10 months after ASCT. In the eight patients evaluable for AQP4 antibodies in the follow-up phase, the pathogenic autoantibodies remained positive after ASCT. Disease-free survival at 3 and 5 years were 31% and 10%, respectively, while progression-free survival at 3 and 5 years were 48%. No secondary malignancy was documented. All patients, but one patient who died from disease progression, are alive at a median follow up of 47 months after ASCT. Conclusions This EBMT retrospective study further demonstrates the potential of ASCT to reduce the highly inflammatory picture typical of NMO, at least in the short term, together with a low incidence of toxicities. Despite transient response after ASCT in the majority of cases, NMO relapsed at later time points underlying the need to investigate maintenance strategies to improve disease outcome in the long term after ASCT. Disclosures: No relevant conflicts of interest to declare.

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