Biomedical subjects

Claudia Lucchinetti

Publications and source records attributed to Claudia Lucchinetti.

6 recordsLinked to original sources

PubMed2006

Remyelination is extensive in a subset of multiple sclerosis patients.

Although spontaneous remyelination does occur in multiple sclerosis lesions, its extent within the global population with this disease is presently unknown. We have systematically analysed the incidence and distribution of completely remyelinated lesions (so-called shadow plaques) or partially remyelinated lesions (shadow plaque areas) in 51 autopsies of patients with different clinical courses and disease durations. The extent of remyelination was variable between cases. In 20% of the patients, the extent of remyelination was extensive with 60-96% of the global lesion area remyelinated. Extensive remyelination was found not only in patients with relapsing multiple sclerosis, but also in a subset of patients with progressive disease. Older age at death and longer disease duration were associated with significantly more remyelinated lesions or lesion areas. No correlation was found between the extent of remyelination and either gender or age at disease onset. These results suggest that the variable and patient-dependent extent of remyelination must be considered in the design of future clinical trials aimed at promoting CNS repair.

Adult↗

PubMed2006

Steroid-responsive encephalopathy associated with autoimmune thyroiditis.

BACKGROUND: Steroid-responsive encephalopathy associated with autoimmune thyroiditis (SREAT), often termed Hashimoto encephalopathy, is a poorly understood and often misdiagnosed entity. OBJECTIVE: To characterize the clinical, laboratory, and radiologic findings in patients with SREAT to potentially improve recognition of this treatable entity. DESIGN: Retrospective analysis of clinical features and diagnostic test data. SETTING: Two affiliated tertiary care referral institutions. PATIENTS: Twenty consecutive (6 male) patients diagnosed as having SREAT from 1995 to 2003. MAIN OUTCOME MEASURES: Clinical features and ancillary test findings associated with SREAT. RESULTS: The median age at disease onset was 56 years (range, 27-84 years). The most frequent clinical features were tremor in 16 (80%), transient aphasia in 16 (80%), myoclonus in 13 (65%), gait ataxia in 13 (65%), seizures in 12 (60%), and sleep abnormalities in 11 (55%). All patients were assigned an alternative misdiagnosis at presentation, most commonly viral encephalitis (n = 5), Creutzfeldt-Jakob disease (n = 3), or a degenerative dementia (n = 4). The most frequent laboratory abnormalities were increased liver enzyme levels in 11, increased serum sensitive thyroid-stimulating hormone levels in 11, and increased erythrocyte sedimentation rate in 5. In only 5 patients (25%) did cerebrospinal fluid abnormalities suggest an inflammatory process. Magnetic resonance imaging abnormalities believed to be related to the encephalopathy were present in 5 patients (26%). CONCLUSIONS: The clinical, laboratory, and radiologic findings associated with SREAT are more varied than previously reported. Misdiagnosis at presentation is common. This treatable syndrome should be considered even if the serum sensitive thyroid-stimulating hormone level and erythrocyte sedimentation rate are normal, the cerebrospinal fluid profile does not suggest an inflammatory process, and neuroimaging results are normal. Until the pathophysiologic mechanism of this and other autoimmune encephalopathies is better characterized, we believe that descriptive terms that reflect an association rather than causation are most appropriate for this syndrome.

Adult↗

PubMed2006

Chemokine receptors as biomarkers in multiple sclerosis.

Leukocyte infiltrates characterize tissue inflammation and are thought to be integral in the pathogenesis of multiple sclerosis (MS). This attribute underlines the importance of understanding mechanisms of leukocyte migration. Chemokines are secreted proteins which govern leukocyte trafficking into targeted organs. Chemokine receptors (CKR) are differentially expressed on leukocytes and their modulation is a potential target for MS disease modifying therapies. Chemokines and their receptors are also potential biomarkers of both disease activity and response to treatment. We describe the fluctuations in CKR expression on peripheral leukocytes in a group of MS patients followed longitudinally for up to 36 months. We observed little fluctuation in CKR expression within each patient over time, despite considerable variability in CKR expression between patients. These observations suggest that individual patients have a CKR set point, and this set point varies from one patient to another. Evaluation of chemokines or chemokine receptors as biomarkers in MS will need to account for this individual variability in CKR expression.

Adult↗

PubMed2004

The pathology of primary progressive multiple sclerosis.

The pathological hallmark of chronic multiple sclerosis includes focal demyelination, gliosis, inflammation and axonal injury. There is limited information on whether these pathological features differ across the clinical phenotypes of the disease (relapsing-remitting, secondary progressive, and primary progressive). This review will focus on the pathological aspects of PPMS and pathogenic implications. A better understanding of the differences in PPMS pathology and pathogenesis will lead to more effective treatment strategies.

Animals↗

PubMed2003

Preferential loss of myelin-associated glycoprotein reflects hypoxia-like white matter damage in stroke and inflammatory brain diseases.

Destruction of myelin and oligodendrocytes leading to the formation of large demyelinated plaques is the hallmark of multiple sclerosis (MS) pathology. In a subset of MS patients termed pattern III, actively demyelinating lesions show preferential loss of myelin-associated glycoprotein (MAG) and apoptotic-like oligodendrocyte destruction, whereas other myelin proteins remain well preserved. MAG is located in the most distal periaxonal oligodendrocyte processes and primary "dying back" oligodendrogliopathy may be the initial step of myelin degeneration in pattern III lesions. In the present study, various human white matter pathologies, including acute and chronic white matter stroke, virus encephalitis, metabolic encephalopathy, and MS were studied. In addition to a subset of MS cases, a similar pattern of demyelination was found in some cases of virus encephalitis as well as in all lesions of acute white matter stroke. Brain white matter lesions presenting with MAG loss and apoptotic-like oligodendrocyte destruction, irrespective of their primary disease cause, revealed a prominent nuclear expression of hypoxia inducible factor-1alpha in various cell types, including oligodendrocytes. Our data suggest that a hypoxia-like tissue injury may play a pathogenetic role in a subset of inflammatory demyelinating brain lesions.

Adolescent↗

PubMed1991

A comparison of cryoprobe and crush lesions in the rat sciatic nerve.

This study examines the behavioral, sensory, motor and structural recovery during the first 2 months following a freeze (cryoprobe) lesion compared to a nerve crush (forceps). There is a complete loss of sensory and motor function following either type of lesion during the first 2 weeks of recovery. The toe spreading reflex and the sciatic functional index of locomotion behavior returned to normal without significant group differences. Latency times for the pain withdrawal reflex were slightly shorter in the cryoprobe group, but both groups returned to baseline during the second month. An improved regenerative pattern was suggested for the motor recovery in the cryoprobe group as expressed by the amplitude of the digital twitch tension curves. However, the respective curve areas were not different. Morphometric analysis indicated a significant reduction in the distal nerve cross-sectional area, an increase in the mean myelinated fiber density and an increase in the estimated total number of myelinated nerve fibers in both experimental groups. Mean fiber diameter and myelin sheath thickness had not fully returned to normal in either experimental group. Both the fiber size and myelin sheath thickness were significantly reduced in the cryoprobe group. In conclusion, the two lesion types have remarkably similar patterns of recovery. Functional data suggest that motor recovery precedes sensory recovery following a cryoprobe lesion.

Animals↗