Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Multiple Sclerosis, Chronic Progressive”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 775 records · Page 43Linked to original sources
PubMed2006

In vivo effects of mitoxantrone on the production of pro- and anti-inflammatory cytokines by peripheral blood mononuclear cells of secondary progressive multiple sclerosis patients.

OBJECTIVE: Mitoxantrone is an antineoplastic agent also used for the treatment of multiple sclerosis (MS). However, despite its efficacy, few data are available on its mechanism of action. The current study was designed to evaluate the short-term (1 month) and long-term (12 months) in vivo effects of mitoxantrone on pro- and anti-inflammatory cytokine production by the peripheral blood mononuclear cells (PBMC) of secondary progressive MS patients. METHODS: Eighteen patients with secondary progressive MS underwent mitoxantrone therapy (at a dose of 12 mg/m(2) once every 3 months) over a 1-year period. Blood samples were obtained at baseline, after 1 month and after 12 months of treatment. The production of cytokines in the PBMC was measured by enzyme-linked immunosorbent assay. RESULTS: There were no significant effects of mitoxantrone on proinflammatory cytokines [interleukin (IL) 6 and IL-12p40] and anti-inflammatory cytokines (IL-10 and transforming growth factor-beta) in our patients. Patients who showed no signs of therapeutic response were characterized by a higher basal PBMC production of IL-6 compared with that of the responding patients (p < 0.05) and mitoxantrone reduced this production after 12 months of treatment (p < 0.05). In the responding patients, IL-10 was significantly increased by mitoxantrone after 12 months of treatment (p < 0.05). CONCLUSION: These findings provide additional information useful in the selection of the patient population suitable for mitoxantrone treatment and suggest that most probably the therapeutic action of mitoxantrone in MS is not entirely mediated by its immunosuppressant effects.

Adult↗
PubMed2005

Soluble vascular cell adhesion molecule (VCAM) is associated with treatment effects of interferon beta-1b in patients with secondary progressive multiple sclerosis.

BACKGROUND: Subcutaneous IFNbeta-1b (Betaferon) is an established immunomodulatory treatment for relapsing remitting MS and active secondary progressive multiple sclerosis (SPMS). It modulates cytokine and adhesion molecule expression but long term in vivo effects of IFNbeta-1b on the immune system are not known in multiple sclerosis. OBJECTIVE: To address the effects of IFNbeta-1b on serum levels for soluble adhesion molecules and cytokine receptors from MS patients. METHODS: Serial blood samples were obtained from 40 patients of the frequent MRI subgroup (20 patients each from the placebo and the IFNbeta-1b treatment group), participating in the European multi-center clinical trial with IFNbeta-1b for secondary progressive MS, at regular intervals for up to 36 months. Soluble adhesion molecules (sVCAM, sICAM-1, sL-Selectin) as well as TNF-receptor I and II were analysed in the serum of patients by enzyme linked immunosorbent assays (ELISAs). Monthly brain MRI was performed in 34 of these patients (16 patients from the placebo and 18 from the IFNbeta-1b group) during months 1-6 and 19-24 to monitor disease activity as assessed by newly occurring gadolinium (Gd) enhancing lesions. RESULTS: An early and significant increase in sVCAM and sTNF-RII serum levels was detected in 16 out of 20 patients (80 %) treated with subcutaneous IFNbeta-1b already at month 1 but was absent in all but one patient during placebo treatment (p < 0.01). Raised sVCAM and TNF RII serum levels during months 1-6 inversely correlated with less MRI activity in the 19-24 months treatment interval in the IFNa-1b treatment group ( p = 0.0093 for TNF-RII; p = 0.047 for VCAM). CONCLUSIONS: sVCAM and sTNF RII levels in the serum of SPMS patients are increased during IFNbeta-1b therapy and may at least in part explain some of the treatment effects, like reduced immune cell transmigration.

Adult↗
PubMed2000

T cell vaccination in secondary progressive multiple sclerosis.

Four secondary progressive MS patients were vaccinated with bovine myelin-reactive irradiated T cell lines from their peripheral blood. Patients were followed for 30-39 months, and monitored for immunological responses toward the vaccine, and for their clinical characteristics. Two patients showed stable EDSS score over time, one patient showed improvement by one EDSS step, and in the remaining patient her EDSS advanced over time. After the second inoculation there was a progressive decline of circulating whole myelin-reactive T cells, MBP143-168, PLP104-117, and MOG43-55-peptide-reactive T cells. In contrast the frequency of tetanus toxoid-reactive T cells remained unchanged. T cell vaccination (TCV) was also associated with a decline of myelin-specific IL-2- and IFN-gamma-secreting T cells. Twelve T cell lines (TCL) that recognize the inoculates were isolated from the peripheral blood of two patients. Ten of these TCL were CD8(+) and lysed the inoculates in a MHC Class I restricted manner. The remaining two TCL were CD4(+), and lysed the inoculates by MHC Class II restricted cytolytic activity. All T cell lines lysed not only myelin-reactive T cells, but also TCL specific for MBP143-168, PLP104-117 and MOG43-55 peptides. Control TCL specific for tetanus toxoid were not lysed. Neutralizing anti-Fas mAb did not influence the killing. Moreover, culture supernatants from two TCL which produce IL-10, were able to block the proliferation of myelin protein-specific TCL. This effect was abrogated using mAbs specific for IL-10. The data obtained indicated that TCV using autologous irradiated bovine myelin-reactive T cells promotes an effective depletion of T cells reactive against different myelin antigens.

Animals↗
PubMed2002

Managing severe lower limb spasticity in multiple sclerosis: does intrathecal phenol have a role?

OBJECTIVE: Established treatment options for managing severe lower limb spasticity and associated pain are of limited value in people with advanced multiple sclerosis (MS). This has resulted in a resurgence of the use of lumbar intrathecal phenol injection (IP). The aim of this study was to investigate the authors' experience with IP. METHODS: This observational study collected cross sectional data from patients with progressive MS who received IP for severe lower limb spasticity. Data from 25 patients were collected prospectively before and after treatment. In 15 cases the data related to the first treatment and in 10 to serial injections. Outcome measures collected included the Ashworth scale, a spasm frequency scale, a pain rating score, and the percentage achievement of practical goals. RESULTS: After injection, all patients demonstrated reduced lower limb tone bilaterally. After the initial injection there was significant improvement on the targeted as compared with the non-targeted side (Wilcoxon rank p=0.003), while no difference in the degree of improvement between the targeted and non-targeted side was seen after serial injections (Wilcoxon rank p=0.731). Twenty four patients were easier to position and 21 had a reduction in their spasm frequency and intensity. Eleven patients with pain reported benefit. Carers found washing and dressing easier in 16 patients and improved safety when using the hoist in 10. Six patients had recurrence of skin breakdown and five patients reported transient adverse changes in their bowel function. CONCLUSIONS: IP can reduce lower limb tone bilaterally after both initial and serial injections. This is most noticeable on the targeted side after initial injection. IP can reduce spasms and pain, leading to improvements in care and overall comfort. IP is an effective treatment option in the management of severe spasticity. Documented selection criteria are essential.

Activities of Daily Living↗
PubMed2002

Correlations between structural CNS damage and functional MRI changes in primary progressive MS.

In patients with primary progressive multiple sclerosis (PPMS), we investigated whether brain and cervical cord structural changes in lesions and normal-appearing brain tissue (NABT), measured using conventional, magnetization transfer (MT), and diffusion tensor (DT) MRI, are correlated with movement-associated cortical activations measured using functional magnetic resonance imaging (fMRI). From 26 right-handed PPMS patients and 15 right-handed, sex- and age-matched healthy controls, we obtained: (a) brain and cervical cord dual-echo scans and MT ratio (MTR) maps; (b) brain mean diffusivity (D(-)) maps, and (c) f-MRI (flexion-extension of the last four fingers of the right hand). All PPMS patients had no previous symptoms affecting their right upper limbs, which were functionally normal. Healthy volunteers showed more significant activation in the ipsilateral cerebellar hemisphere than PPMS patients. PPMS patients showed greater activation bilaterally in the superior temporal gyrus, ipsilaterally in the middle frontal gyrus, and, contralaterally in the insula/claustrum. In PPMS patients, moderate to strong correlations (r values ranging from 0.59 to 0.68) were found between relative activations of cortical areas located in a widespread network for sensory-motor and multimodal integration and the severity of structural changes of the NABT (as measured using MT and DT MRI) and the severity of cervical cord damage (as measured using MT MRI). This study shows that the pattern of cortical activation of PPMS patients is different from that of normal controls even when performing a motor task with clinically unaffected limbs. It also suggests that cortical reorganization might be able to limit the consequences of MS injury in the brain and cervical cord.

Adult↗
PubMed2001

Autologous hematopoietic stem cell transplantation suppresses Gd-enhanced MRI activity in MS.

BACKGROUND: Autologous hematopoietic stem cell transplantation (ASCT) has been recently utilized with encouraging results in patients with poorly controlled MS. OBJECTIVE: To determine in severe cases of MS the effect of ASCT on gadolinium (Gd)-enhanced MRI and to obtain information on clinical course and safety. METHODS: In a cooperative study, 10 patients with rapidly evolving secondary progressive MS were transplanted, after BEAM conditioning regimen (carmustine, etoposide, cytosine-arabinoside, and melphalan), with unmanipulated autologous peripheral blood SC mobilized with high-dose cyclophosphamide (CY; 4 g/m2) and granulocyte-colony-stimulating factor. Triple-dose Gd-enhanced scans were performed monthly for a pretreatment period of 3 months and compared with serial monthly Gd-enhanced MRI for the following 6 months and then once every 3 months. RESULTS: The median follow-up is now 15 months (range 4 to 30 months). The number of Gd-enhancing lesions decreased immediately after mobilization with CY and finally dropped to zero in all cases after the conditioning regimen. The number of new T2-weighted positive lesions paralleled data obtained for Gd-enhanced MRI. Clinically, patients improved slightly or remained stable. CONCLUSION: These results demonstrate that the therapeutic sequence CY-BEAM-ASCT has the capacity to completely suppress MR-enhancing activity, an effect that is sustained with time. The final impact of this procedure on disease course remains to be established.

Adult↗
PubMed2006

Innate immunity in multiple sclerosis: myeloid dendritic cells in secondary progressive multiple sclerosis are activated and drive a proinflammatory immune response.

Multiple sclerosis (MS) is postulated to be a T cell-mediated autoimmune disease characterized clinically by a relapsing-remitting (RR) stage followed by a secondary progressive (SP) phase. The progressive phase is felt to be secondary to neuronal degenerative changes triggered by inflammation. The status of the innate immune system and its relationship to the stages of MS is not well understood. Dendritic cells (DCs) are professional APCs that are central cells of the innate immune system and have the unique capacity to induce primary immune responses. We investigated circulating myeloid DCs isolated directly from the blood to determine whether there were abnormalities in myeloid DCs in MS and whether they were related to disease stage. We found that SP-MS subjects had an increased percentage of DCs expressing CD80, a decreased percentage expressing PD-L1, and an increased percentage producing IL-12 and TNF-alpha compared with RR-MS or controls. A higher percentage of DCs from both RR and SP-MS patients expressed CD40 compared with controls. We then investigated the polarization effect of DCs from MS patients on naive T cells taken from cord blood using a MLR assay. Whereas DCs from RR-MS induced higher levels of Th1 (IFN-gamma, TNF-alpha) and Th2 (IL-4, IL-13) cytokines compared with controls, DCs from SP-MS only induced a polarized Th1 response. These results demonstrate abnormalities of DCs in MS and may explain the immunologic basis for the different stages and clinical patterns of MS.

Adult↗
PubMed2006

Regional gray matter atrophy in early primary progressive multiple sclerosis: a voxel-based morphometry study.

BACKGROUND: Gray matter (GM) atrophy has been reported in multiple sclerosis (MS). However, little is known about its regional distribution. OBJECTIVE: To investigate the regional distribution of GM atrophy in clinically early primary progressive MS (PPMS). DESIGN AND PATIENTS: Thirty-one patients with PPMS within 5 years of symptom onset (mean age, 43.2 years; median Expanded Disability Status Scale score, 4.5) and 15 healthy control subjects (mean age, 43.7 years) were studied. All subjects underwent a 3-dimensional inversion-recovery fast spoiled gradient-recalled echo sequence that was repeated after 1 year in patients only. Magnetic resonance images underwent an optimized voxel-based morphometric analysis that segments magnetic resonance data volumes in a normalized space and quantifies tissue atrophy on a voxel-by-voxel basis. A lesion mask was created for each patient and used in normalization and segmentation steps to minimize bias from lesions. A multisubject design was used in the cross-sectional study to compare patients with PPMS and controls. A 1-way analysis of variance (within-subjects) design was used in the longitudinal study. RESULTS: At baseline, patients with PPMS displayed bilateral thalamic atrophy compared with controls. In addition, a significant association between lesion load and decreased GM volume was found for the thalami. Loss of GM in the putamen, caudate, thalami, and cortical and infratentorial areas was observed in patients after 1 year of follow-up. CONCLUSIONS: Atrophy is most obvious in deep GM in clinically early PPMS. This may reflect increased sensitivity of these regions to neurodegeneration. Cortical and infratentorial atrophy developed as the disease evolved.

Adult↗
PubMed2001

Randomized controlled trial of interferon-beta-1a in secondary progressive MS: MRI results.

OBJECTIVE: To examine MRI changes resulting from treatment of secondary progressive MS (SPMS) with two doses of interferon-beta-1a (Rebif). BACKGROUND: Interferon-beta (IFN-beta) reduces relapses and delays progression in relapsing-remitting MS, but there are conflicting results on its clinical benefit in SPMS. METHODS: In a double-blind, randomized, multicenter, placebo-controlled study (SPECTRIMS), 618 patients received IFN-beta-1a 22 microg, 44 microg, or placebo subcutaneously three times weekly for 3 years. T2 activity and burden of disease (BOD) were measured in 617 patients by using semiannual proton density/T2-weighted (PD/T2) MRI scans. A cohort of 283 patients also had 11 monthly PD/T2 and T1-weighted gadolinium-enhanced (T1-Gd) scans at study start. RESULTS: Treatment reduced median numbers of active lesions per patient per scan (semiannual T2 activity: 0.17, 0.20 and 0.67 for the high dose, low dose, and placebo, p < 0.0001; monthly combined unique activity [T1+T2]: 0.11, 0.22, and 1.00, p < 0.0001) and accumulation of BOD (percent change from baseline to month 36: -1.3, -0.5, and 10.0 for the high dose, low dose, and placebo, respectively; p = 0.0001). MRI benefit was most evident in the subgroup of patients who reported relapses in the 2 years before the study. Neutralizing antibody development was associated with reduction in treatment effect: antibody-positive patients did not show significant differences from placebo at either dose. CONCLUSIONS: Interferon-beta-1a used in SPMS showed significant effects on all MRI measures, particularly in patients with relapses in the 2 years before the study.

Adjuvants, Immunologic↗
PubMed2006

Immunological studies of mitoxantrone in primary progressive MS.

Mitoxantrone (MX) has demonstrated efficacy in multiple sclerosis (MS), but its immunologic mechanisms of action are poorly understood. Furthermore, no study has examined the immunological effects of MX in primary progressive MS (PPMS). This study investigated the immunological effects of MX therapy in PPMS patients. Lymphocyte phenotypes and chemokine receptor (CCR) expression were evaluated by flow cytometry on fresh PBMC from 20 PPMS patients enrolled in a placebo (PLC)-controlled trial of MX. Longitudinal data were collected at weeks 0, 12, 24, 36 and short-term data (pre-/post-infusion) were collected at weeks 0 and 36. CXCR3, CCR1, CCR2 and CCR5 on CD4 and CD8 T cells and CD14 monocytes were evaluated. MX therapy induced a significant increase in the proportion of CD8 T cells (CD45RO(-)) over 9 months. Expression of several CCR increased following MX treatment. Two of the eight MX-treated patients demonstrated dramatic upregulation (70-76%) of CCR2 on monocytes. These two patients were the only MX-treated patients to demonstrate active inflammation by magnetic resonance imaging (MRI). PLC patients did not show significant changes in CCR expression. MX therapy was not associated with selective loss of CD4, CD8 or CD14 cells 1 month after treatment or over 9 months. These results suggest that MX therapy leads to a longitudinal increase in CD8 T cells and may increase CCR in patients with inflammation on MRI. Overall, MX did not show extensive immune changes in PPMS, although patients with active disease (gadolinium enhancing lesions) may identify a subset of PPMS subjects who respond immunologically to MX therapy. An improved understanding of MX may help identify markers of disease activity and response to therapy.

Adult↗
PubMed2003

The normal appearing grey matter in primary progressive multiple sclerosis: a magnetisation transfer imaging study.

BACKGROUND: In 10-15 % of patients with multiple sclerosis (MS), the clinical course is characterized by slow progression in disability without relapses (primary progressive (PP) MS). The mechanism of disability in this form of MS is poorly understood. Using magnetization transfer ratio (MTR) imaging, we investigated normal appearing white matter (NAWM) and normal appearing grey matter (NAGM) in PPMS and explored the relationship of MTR measures with disability. METHODS: Thirty patients with PPMS and 30 age matched controls had spin echo based MTR imaging to study lesions and normal appearing tissues. The brain was segmented into NAWM and NAGM using SPM99 with lesions segmented using a semiautomated local thresholding technique. A 75% probability threshold for classification of NAWM and NAGM was used to diminish partial volume effects. From normalized histograms of MTR intensity values, six MTR parameters were measured. Mean lesion MTR and T2 lesion volume were also measured. Disability was assessed using Kurtzke's expanded disability status scale (EDSS). RESULTS: Compared with controls, patients exhibited a significant reduction in mean NAWM (p = 0.001) and NAGM (p = 0.004) MTR. Spearman's rank correlation of EDSS with the six MTR parameters in NAWM and NAGM, mean lesion MTR, and T2 lesion volume, was only significant with mean NAGM MTR (r = -0.41, p = 0.02), the 25th percentile of NAGM MTR intensity (r = -0.37, p = 0.05), and T2 lesion volume (r = 0.39, p = 0.04). Multiple regression analysis of the relationship between EDSS and 4 MR parameters representing each tissue type (mean NAWM MTR, mean NAGM MTR, mean lesion MTR, T2 lesion volume) showed that the association of EDSS with mean NAGM MTR remained significant. CONCLUSIONS: There appear to be significant abnormalities in the NAGM in PP MS. Further investigation of the pathological basis and functional significance of grey matter abnormality in PPMS is warranted.

Adult↗
PubMed2005

Axonal injury and overall tissue loss are not related in primary progressive multiple sclerosis.

BACKGROUND: There is an increasing body of evidence that magnetic resonance imaging-occult tissue damage is an important component of primary progressive multiple sclerosis (PPMS) pathology. Proton magnetic resonance spectroscopy (1H-MRS) can be used to measure in vivo whole-brain N-acetylaspartate (WBNAA) concentrations, the decrease of whose levels is considered a marker of neuronal-axonal injury. OBJECTIVES: To study WBNAA 1H-MRS as a tool to provide information about irreversible brain damage in PPMS and to investigate the relationship between WBNAA and other magnetic resonance imaging measures of MS disease burden, including brain atrophy. METHODS: The following magnetic resonance pulse sequences of the brain were obtained from 32 patients with PPMS and 16 age-matched healthy subjects: (1) dual-echo turbo spin-echo; (2) T1-weighted spin-echo; and (3) 1H-MRS to measure WBNAA concentration. Brain total lesion volumes were measured. Normalized brain volumes were calculated using a fully automated technique. Absolute WBNAA amounts were calculated using a phantom replacement method and were then corrected for individual subjects' brain size. RESULTS: Levels of WBNAA concentrations and normalized brain volumes were significantly lower in patients with PPMS (mean values, 10.2 mm and 1500.0 mL, respectively) than in healthy controls (mean values, 12.9 mm and 1585.2 mL). Both WBNAA concentrations and normalized brain volumes were included as independent factors in the final model of a multivariable analysis predicting the subjects' condition. No significant correlations were found between WBNAA values and normalized brain volumes, WBNAA and T2-weighted or T1-weighted lesion volumes. CONCLUSIONS: Axonal-neuronal damage in the brain of patients with PPMS seems to occur, at least partially, independently of the burden of magnetic resonance imaging-visible lesions. Whole-brain N-acetylaspartate values and normalized brain volumes were unrelated in this cohort, thereby suggesting that 1H-MRS and atrophy assessment may provide in vivo complementary information about the actual extent of brain damage in PPMS.

Adult↗
PubMed2004

Escalating immunotherapy of multiple sclerosis--new aspects and practical application.

Recent clinical studies in multiple sclerosis (MS) provide new data on the treatment of clinically isolated syndromes, on secondary progression, on direct comparison of immunomodulatory treatments and on dosing issues. All these studies have important implications for the optimized care of MS patients. The multiple sclerosis therapy consensus group (MSTCG) critically evaluated the available data and provides recommendations for the application of immunoprophylactic therapies. Initiation of treatment after the first relapse may be indicated if there is clear evidence on MRI for subclinical dissemination of disease. Recent trials show that the efficacy of interferon beta treatment is more likely if patients in the secondary progressive phase of the disease still have superimposed bouts or other indicators of inflammatory disease activity than without having them. There are now data available, which suggest a possible dose-effect relation for recombinant beta-interferons. These studies have to be interpreted with caution, as some potentially important issues in the design of these studies (e. g. maintenance of blinding in the clinical part of the study) were not adequately addressed. A meta-analysis of selected interferon trials has been published challenging the value of recombinant IFN beta in MS. The pitfalls of that report are discussed in the present review as are other issues relevant to treatment including the new definition of MS, the problem of treatment failure and the impact of cost-effectiveness analyses. The MSTCG panel recommends that the new diagnostic criteria proposed by McDonald et al. should be applied if immunoprophylactic treatment is being considered. The use of standardized clinical documentation is now generally proposed to facilitate the systematic evaluation of individual patients over time and to allow retrospective evaluations in different patient cohorts. This in turn may help in formulating recommendations for the application of innovative products to patients and to health care providers. Moreover, in long-term treated patients, secondary treatment failure should be identified by pre-planned follow-up examinations, and other treatment options should then be considered.

Clinical Trials as Topic↗
PubMed2002

Thalamic neurodegeneration in multiple sclerosis.

Multiple sclerosis is still regarded primarily as a disease of the white matter. However, recent evidence suggests that there may be significant involvement of gray matter. Here, we have used magnetic resonance imaging and magnetic resonance spectroscopy in vivo and histopathology postmortem to estimate thalamic neuronal loss in patients with multiple sclerosis. Our results show that neuronal loss in multiple sclerosis can be substantial (30-35% reduction). We conclude that a neurodegenerative pathology may make a major contribution to the genesis of symptoms in multiple sclerosis.

Adult↗
PubMed2004

[Autoimmune functional disorders of the thyroid during interferon-beta-1b treatment in patients with multiple sclerosis. Case report and literature review].

Occurrence of thyroid autoimmunity and dysfunction following interferon alpha treatment of viral hepatitis and other diseases are known adverse effects and have been ascribed to the cytokine's general immunomodulatory and -activating properties. However, in spite of its extensive application, there have been few reports of such incidents during interferon beta (IFN-beta-1a/b) therapy, which is considered the standard treatment of relapsing-remitting multiple sclerosis (MS), and prospective studies have been published only recently. Here we present the case of a 38-year-old woman with Graves' disease including massive thyroid-associated ophthalmopathy appearing de novo following IFN-beta-1b therapy for MS. A literature search revealed an 11% (5% clinically overt) overall incidence of de novo thyroid dysfunction in IFN-beta-treated MS patients, mostly autoimmune hyperthyroidism. (Large-scale comparative studies for IFN-beta-1a are not available at present). Specific treatment but not necessarily discontinuation of IFN-beta-1b therapy was required in most cases. Female gender, pre-existing thyroid autoimmunity, and family history of thyroid disorders are presumable risk factors for thyroid dysfunction de novo during IFN-beta-1b treatment.

Adult↗
PubMed2002

Reversible MRI changes of hypothalamus in a multiple sclerosis patient with homeostatic disturbances.

Multiple sclerosis (MS) patients occasionally present with homeostatic disturbances suggestive of hypothalamic dysfunction; however, the hypothalamus often appears normal on imaging, apart from confirmation in a few necropsy studies. In this article we describe a Chinese woman with atypical clinical presentation. She presented with relapsing symptoms and signs consistent with hypothalamic dysfunction including hyperprolactinema, syndrome of inappropriate secretion of anti-diuretic hormone (SIADH), hypersomnolence and temperature dysregulation. Serial MRI depicted the atypical reversible changes in the hypothalamus, correlating with the observed homeostatic abnormalities.

Female↗