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Biomedical subjects

Dean M Wingerchuk

Publications and source records attributed to Dean M Wingerchuk.

At least 19 recordsLinked to original sources
PubMed2007

Diagnosis and treatment of neuromyelitis optica.

BACKGROUND: Neuromyelitis optica (NMO) is an uncommon CNS demyelinating syndrome often mistaken for severe multiple sclerosis (MS). Several clinical, laboratory, and neuroimaging characteristics may accurately distinguish NMO from MS early in the disease course. REVIEW SUMMARY: NMO is usually a relapsing disorder associated with early, severe, attack-related residual disability. It is associated with a highly specific antibody marker, NMO-IgG, which targets the water channel aquaporin-4. Revised NMO diagnostic criteria require optic neuritis, acute myelitis, and 2 of the following 3 characteristics: disease-onset brain magnetic resonance imaging (MRI) that is nondiagnostic for MS, contiguous spinal cord MRI lesion extending over 3 or more vertebral segments, and NMO-IgG seropositive status. Symptoms referable to central nervous system regions other than the optic nerve and spinal cord do not necessarily exclude the diagnosis of NMO, nor does the presence of brain MRI lesions. NMO-IgG has facilitated an appreciation that the spectrum of NMO is wider than previously recognized, and includes a proportion of patients with each of recurrent longitudinally extensive myelitis, recurrent isolated optic neuritis, and Japanese opticospinal MS. In contrast to typical MS, clinical experience and case series suggest that NMO requires long-term immunosuppressive therapy. CONCLUSIONS: NMO can be reliably differentiated from MS at an early stage using validated diagnostic criteria. The spectrum of NMO is wider than previously appreciated. Accurate, early diagnosis is critical to facilitate initiation of immunosuppressive therapy for attack prevention.

Humans↗
PubMed2007

Treatment of vascular dementia and vascular cognitive impairment.

OBJECTIVE: In patients with vascular dementia and vascular cognitive impairment, are acetylcholinesterase inhibitors (donepezil, galantamine, and rivastigmine) and N-methyl-d-aspartate (NMDA) receptor antagonists (memantine) effective in improving cognitive function over placebo? METHODS: The question was addressed with a structured, evidence-based, clinical, neurologic practice review. Participants included consultant and resident neurologists, clinical epidemiologists, medical librarians, and clinical content experts. A critically appraised topic format was employed, with a clinical scenario, structured question, search strategy, appraisal, results, summary of evidence, commentary, and bottom-line conclusions. RESULTS: Eight relevant systematic reviews and randomized controlled trials were identified and served as the principal sources of information. The best evidence to date revealed that donepezil 5 mg/d [number needed to treat (NNT) = 10] was the most effective and best tolerated [number needed to harm (NNH) = 50] of the available agents. Galantamine 24 mg/d (NNT = 7) was also effective but less well tolerated (NNH = 7). Due to insufficient evidence, rivastigmine could not yet be recommended for the treatment of vascular dementia. Memantine appeared to be safe and well tolerated but did not demonstrate effectiveness across all cognitive outcomes and clinical global measures. CONCLUSION: Acetylcholinesterase inhibitors and NMDA receptor antagonists, in general, displayed promise as treatments for patients with vascular dementia and vascular cognitive impairment. The most effective, evidence-based treatments were donepezil and galantamine.

Aged↗
PubMed2006

Brain abnormalities in neuromyelitis optica.

BACKGROUND: Neuromyelitis optica (NMO) is a severe demyelinating disease defined principally by its tendency to selectively affect optic nerves and the spinal cord causing recurrent attacks of blindness and paralysis. Contemporary diagnostic criteria require absence of clinical disease outside the optic nerve or spinal cord. We have, however, frequently encountered patients with a well-established diagnosis of NMO in whom either asymptomatic or symptomatic brain lesions develop suggesting that the diagnostic criteria for NMO should be revised. OBJECTIVE: To describe the magnetic resonance image (MRI) brain findings in NMO. DESIGN: Observational, retrospective case series. Patients We ascertained patients through a clinical biospecimens database of individuals with definite or suspected NMO. We included patients who (1) satisfied the 1999 criteria of Wingerchuk et al for NMO except for the absolute criterion of lacking symptoms beyond the optic nerve and spinal cord and the supportive criterion of having a normal brain MRI at onset; (2) had MRI evidence of a spinal cord lesion extending 3 vertebral segments or more (the most specific nonserological feature to differentiate NMO from MS); and (3) were evaluated neurologically and by brain MRI at the Mayo Clinic. MAIN OUTCOME MEASURES: Magnetic resonance images were classified as normal or as abnormal with either nonspecific, multiple sclerosis-like or atypical abnormalities. We evaluated whether brain lesions were symptomatic and analyzed the neuropathologic features of a single brain biopsy specimen. RESULTS: Sixty patients (53 women [88%]) fulfilled these inclusion criteria. The mean +/- SD age at onset was 37.2 +/- 18.4 years and the mean +/- SD duration of follow-up was 6.0 +/- 5.6 years. Neuromyelitis optica-IgG was detected in 41 patients (68%). Brain MRI lesions were detected in 36 patients (60%). Most were nonspecific, but 6 patients (10%) had multiple sclerosis-like lesions, usually asymptomatic. Another 5 patients (8%), mostly children, had diencephalic, brainstem or cerebral lesions, atypical for multiple sclerosis. When present, symptoms of brain involvement were subtle, except in 1 patient who was comatose and had large cerebral lesions. CONCLUSIONS: Asymptomatic brain lesions are common in NMO, and symptomatic brain lesions do not exclude the diagnosis of NMO. These observations justify revision of diagnostic criteria for NMO to allow for brain involvement.

Adult↗
PubMed2006

Premenstrual multiple sclerosis pseudoexacerbations: Role of body temperature and prevention with aspirin.

BACKGROUND: Many women with multiple sclerosis (MS) experience transient neurologic symptom worsening and fatigue in conjunction with the menstrual cycle. Aspirin reduces MS fatigue in some patients. OBJECTIVE: To describe 3 women with MS who experienced stereotypic, temperature-independent neurologic symptoms and diurnal fatigue in the mid-to-late luteal phase of the menstrual cycle. Aspirin treatment prevented the symptoms. DESIGN AND SETTING: Case series at the Mayo Clinic outpatient MS clinics, Scottsdale, Ariz, and Rochester, Minn. PATIENTS: Three women with relapsing-remitting MS. INTERVENTIONS: Body temperature measurement, symptom diary, and oral aspirin. MAIN OUTCOME MEASURES: Body temperature, Modified Fatigue Impact Scale, and evaluation of neurologic symptoms and signs. RESULTS: Morning oral body temperature did not differ during symptomatic vs asymptomatic portions of the luteal phase (P = .55). Aspirin (650 mg twice daily) prevented symptoms but did not significantly alter the luteal phase body temperature. CONCLUSIONS: Aspirin prophylaxis may prevent luteal phase-associated MS pseudoexacerbations. However, the observed relationship between the luteal menstrual phase and MS symptom worsening is not fully explained by thermoregulation, which implicates other hormonal or immunologic mechanisms.

Administration, Oral↗
PubMed2006

Neuromyelitis optica brain lesions localized at sites of high aquaporin 4 expression.

BACKGROUND: Neuromyelitis optica (NMO)-IgG is a specific autoantibody marker for NMO. It binds selectively to aquaporin 4 (AQP4), which is highly concentrated in astrocytic foot processes at the blood-brain barrier and is not restricted to optic nerve and spinal cord. Although it is conventionally believed that the brain is spared, brain imaging abnormalities are not uncommon in patients with NMO. OBJECTIVE: To investigate the location of brain lesions that are distinctive for NMO with respect to the localization of AQP4 in mammalian brain. DESIGN: Observational, retrospective case series. SETTING: Clinical serologic cohort of patients tested for NMO-IgG for whom brain MRI images were available. PATIENTS: We identified 120 patients seropositive for NMO-IgG for whom brain magnetic resonance images were available. MAIN OUTCOME MEASURE: Magnetic resonance imaging abnormalities. RESULTS: In 8 patients we observed recurring and distinctive magnetic resonance imaging abnormalities in the hypothalamic and periventricular areas that corresponded to brain regions of high AQP4 expression. CONCLUSION: The distribution of NMO-characteristic brain lesions corresponds to sites of high AQP4 expression.

Adolescent↗
PubMed2006

Neuromyelitis optica IgG predicts relapse after longitudinally extensive transverse myelitis.

OBJECTIVE: We investigated whether neuromyelitis optica (NMO) IgG seropositivity at the initial presentation of longitudinally extensive transverse myelitis (LETM) predicts relapse of myelitis or development of optic neuritis. METHODS: Prospective study of patients with initial LETM who were tested for the presence of NMO-IgG. RESULTS: Eleven of 29 patients (37.9%) were seropositive after a first attack of LETM spanning three or more vertebral segments on magnetic resonance imaging. Of 23 patients followed up for 1 year, none of 14 who were seronegative experienced a relapse or developed optic neuritis. Of 9 seropositive patients, 5 developed a second event: 4 of 9 (44%) developed recurrent transverse myelitis and 1 of 9 (11%) developed optic neuritis (p = 0.004). INTERPRETATION: LETM represents an inaugural or limited form of NMO in a high proportion of patients. The 40% of patients who are seropositive for NMO-IgG are at high risk for relapse.

Adult↗
PubMed2006

NMO-IgG: a specific biomarker for neuromyelitis optica.

Neuromyelitis optica (NMO) is an inflammatory demyelinating disease that principally targets the optic nerves and spinal cord and often leads to severe disability and occasionally life threatening respiratory failure. Although its clinical manifestations overlap with those of multiple sclerosis (MS), in established cases these two conditions can be distinguished on the basis of clinical, radiological, and routine spinal fluid studies. The diagnosis in early cases or limited forms of NMO is difficult. We recently discovered a unique IgG autoantibody (NMO-IgG) that is highly specific to patients with NMO and thus a valuable diagnostic aid. Its antigen, aquaporin-4 (AQP4), is the central nervous system's predominant water channel protein. This antibody has not yet been proven to be pathogenic, but several facts suggest that it might be, including the similarity of the immunohistochemical pattern of NMO-(AQP4) IgG binding to mouse CNS tissues to the pattern of immune complex deposition in autopsied patients' spinal cord tissue. The spectrum of diseases identified by NMO-IgG is broader than has previously been recognized clinically and includes incomplete forms of NMO, such as recurrent transverse myelitis without optic neuritis and recurrent optic neuritis without myelitis.

Autoantibodies↗
PubMed2006

The clinical course of acute disseminated encephalomyelitis.

The objective of this review is to describe recent advances in understanding the clinical course of pediatric and adult acute disseminated encephalomyelitis (ADEM), especially the risk of relapse and conversion to multiple sclerosis (MS). The diagnosis of ADEM is reached on clinical grounds, typically in the setting of a post-infectious meningoencephalitic syndrome associated with multifocal neurological symptoms and signs, magnetic resonance imaging (MRI) evidence of white matter lesions and exclusion of other causes. Although typically monophasic, several case series demonstrate 'multiphasic' or 'recurrent' forms of ADEM with clinical relapses occurring within a short interval of disease onset. Furthermore, the estimated risk of developing MS is substantial for both children (0-33%) and adults (approximately 35%). Advances in neuroimaging have identified some MRI features that have predictive value for a relapsing course but they are not accurate enough for therapeutic decision-making; a diagnosis of monophasic ADEM should be made with caution in all cases, especially those presenting in adulthood. Research in ADEM and related disorders remains hampered by lack of prospective studies, specific and reproducible clinical case definitions and variable follow-up methods. Standardization of these variables would facilitate identification of more accurate diagnostic and prognostic variables, discovery and testing of potential objective biomarkers that would, in turn, allow early prediction of a relapsing course and appropriate therapeutic interventions.

Encephalomyelitis, Acute Disseminated↗
PubMed2006

Evidence for humoral autoimmunity in neuromyelitis optica.

Neuromyelitis optica (NMO) is an idiopathic central nervous system (CNS) demyelinating syndrome that may be distinguished from typical multiple sclerosis (MS). Although the cause of the disorder is not known, several lines of evidence suggest that the fundamental immunological process is driven by humoral mechanisms. These observations include the frequent coexistence of systemic autoimmune disease or positive serum autoantibodies with NMO, immunopathologic studies that demonstrate prominent complement activation and immunoglobulin deposition and the discovery of the serum autoantibody NMO-IgG, a potential NMO biomarker that targets aquaporin-4. Furthermore, clinical experience suggests that plasmapheresis and immunosuppressive therapies are beneficial for treatment and prevention of acute attacks but that standard MS immunomodulatory drugs may not alter the course of NMO. This evidence is reviewed in the context of its implications for future laboratory and clinical research in NMO.

Animals↗
PubMed2006

Multiple sclerosis disease-modifying therapies: adverse effect surveillance and management.

There are five approved, partially effective, parenteral disease-modifying therapies for multiple sclerosis (MS), including three interferon-beta preparations, glatiramer acetate and the antineoplastic agent mitoxantrone. A sixth drug, natalizumab, was withdrawn from the market in 2005 but could return with increased safety measures. Careful surveillance for, and management of, the minor and serious adverse effects associated with these therapies in routine practice provides the best opportunity for maintaining compliance and achieving maximal therapeutic efficacy. This review outlines the strategies for the prevention, identification and management of the complications associated with administration and ongoing use of current MS therapies. These skills will become increasingly important to those caring for MS patients as contemporary treatment regimens become increasingly complex.

Adverse Drug Reaction Reporting Systems↗
PubMed2005

Spinal cord astrocytoma presenting as "idiopathic" intracranial hypertension.

Increased intracranial pressure is rarely seen in association with spinal tumors. We describe a young, non-obese man who presented with increased intracranial pressure, papilledema and visual obscuration. Multiple cerebrospinal fluid (CSF) examinations with normal or minimally elevated CSF protein lead to the initial diagnosis of idiopathic intracranial hypertension. After a lumboperitoneal shunt placement a progressive thoracic myelopathy developed 7 months after onset of symptoms. The spinal MRI showed a low cervical-upper thoracic intramedullary tumor. Open biopsy confirmed a grade 3 fibrillary astrocytoma. The suspected mechanisms of spinal tumors causing increased intracranial pressure are reviewed as well as three other cases of spinal astrocytomas previously reported in the literature that presented with papilledema and increased intracranial pressure without hydrocephalus. This case illustrates that increased intracranial pressure may in exceptional cases of spinal tumors precede the more typical myelopathic presentation by months and mimic idiopathic intracranial hypertension.

Adult↗
PubMed2005

Neuromyelitis Optica.

Neuromyelitis optica (Devic's syndrome) is an uncommon, idiopathic, demyelinating syndrome of the central nervous system that preferentially affects the optic nerves and spinal cord. It frequently is misdiagnosed as severe multiple sclerosis, but usually is readily distinguished from multiple sclerosis in fully developed cases because of its severity, typical magnetic resonance imaging (MRI) findings (normal brain MRI; longitudinally extensive lesions on spinal cord MRI), and cerebrospinal fluid analysis (polymorphonuclear pleocytosis and absence of oligoclonal banding). A serum autoantibody marker, NMO-IgG, is highly specific for the disorder. Most patients have relapsing disease, and natural history studies confirm early and severe disability. We treat acute myelitis and optic neuritis exacerbations with parenteral corticosteroids and use rescue plasmapheresis for severe, refractory attacks. Immunomodulatory drugs used for typical multiple sclerosis seem ineffective for relapse prevention. We recommend systemic immunosuppression, usually with azathioprine and oral corticosteroids, for most patients. Fulminant disease and breakthrough disease may respond to other forms of humoral immunotherapy such as rituximab.

Journal Article↗