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Dean M Wingerchuk

Publications and source records attributed to Dean M Wingerchuk.

10 recordsLinked to original sources
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↗
PubMed2004

Neuromyelitis optica: current concepts.

Neuromyelitis optica (NMO; Devic's syndrome or Devic's disease) is a clinically defined disorder consisting of optic neuritis (ON) in combination with myelitis. Its nosological relationship to other central nervous system demyelinating diseases remains uncertain. Advances in understanding of its natural history and pathophysiology may eventually allow determination of whether idiopathic NMO represents a specific disease. This article summarizes recent progress in these areas of NMO research.

Humans↗
PubMed2004

Seizure prophylaxis in patients with brain tumors: a meta-analysis.

OBJECTIVE: To assess whether antiepileptic drugs (AEDs) should be prescribed to patients with brain tumors who have no history of seizures. METHODS: We performed a meta-analysis of randomized controlled trials (1966-2004) that evaluated the efficacy of AED prophylaxis vs no treatment or placebo to prevent seizures in patients with brain tumors who had no history of epilepsy. Summary odds ratios (ORs) were calculated using a random-effects model. Three subanalyses were performed to assess pooled ORs of seizures in patients with primary glial tumors, cerebral metastases, and meningiomas. RESULTS: Of 474 articles found in the initial search, 17 were identified as primary studies. Five trials met inclusion criteria: patients with a neoplasm (primary glial tumors, cerebral metastases, and meningiomas) but no history of epilepsy who were randomized to either an AED or placebo. The 3 AEDs studied were phenobarbital, phenytoin, and valproic acid. Of the 5 trials, 4 showed no statistical benefit of seizure prophylaxis with an AED. Meta-analysis confirmed the lack of AED benefit at 1 week (OR, 0.91; 95% confidence interval [CI], 0.45-1.83) and at 6 months (OR, 1.01; 95% CI, 0.51-1.98) of follow-up. The AEDs had no effect on seizure prevention for specific tumor pathology, including primary glial tumors (OR, 3.46; 95% CI, 0.32-37.47), cerebral metastases (OR, 2.50; 95% CI, 0.25-24.72), and meningiomas (OR, 0.62; 95% CI, 0.10-3.85). CONCLUSIONS: No evidence supports AED prophylaxis with phenobarbital, phenytoin, or valproic acid in patients with brain tumors and no history of seizures, regardless of neoplastic type. Subspecialists who treat patients with brain tumors need more education on this issue. Future randomized controlled trials should address whether any of the newer AEDs are useful for seizure prophylaxis.

Anticonvulsants↗
PubMed2003

Neuromyelitis optica: clinical predictors of a relapsing course and survival.

BACKGROUND: The relapsing form of neuromyelitis optica (NMO) is characterized by recurrent optic neuritis and myelitis, usually leading to severe, permanent, relapse-related neurologic impairment (e.g., blindness, paraplegia) within 5 years. Aggressive therapy aimed at relapse prevention initiated soon after disease onset may be expected to have a relatively greater impact on early relapse-related disability in NMO than in typical MS. Early prediction of a relapsing course and subsequent disease severity would facilitate design and implementation of clinical trials of such therapies. METHODS: A database of clinical and laboratory features of patients with NMO (n = 80) was used to develop potentially useful models predictive of a relapsing disease course and of subsequent disease severity as measured by survival. RESULTS: Predictors of a relapsing course were longer interattack interval between the first two clinical events (rate ratio [RR] = 2.16; per month increase), older age at onset (RR = 1.08; per year increase), female sex (RR = 10.0, female vs male), and less severe motor impairment with the sentinel myelitis event (RR = 0.48; per severity scale point increase). A history of other autoimmune disease (RR = 4.15; presence vs absence), higher attack frequency during the first 2 years of disease (RR = 1.21; per attack), and better motor recovery following the index myelitis event (RR = 1.84; per point increase) were associated with mortality due to relapsing NMO. CONCLUSIONS: These predictive models identify several clinical features, each available at diagnosis or early in the disease course, that predict relapsing disease and survival. These results may be useful to identify patients at high risk for severe, relapsing neuromyelitis optica in order to initiate early therapy for relapse prevention and to design clinical trials to study such interventions.

Adolescent↗
PubMed2003

Postinfectious encephalomyelitis.

Postinfectious forms of encephalomyelitis, also termed acute disseminated encephalomyelitis (ADEM), form one of several categories of inflammatory demyelinating disorders of the central nervous system (CNS). Recent large, retrospective case series have refined our understanding of the clinical, laboratory, and neuroimaging characteristics of ADEM. The differences between childhood and adult ADEM, risks of development of multiple sclerosis, and the contributions of recent studies to refining the nosology of CNS demyelinating syndromes are discussed.

Adolescent↗
PubMed2003

Practical consultations: multiple sclerosis.

People with multiple sclerosis (MS) are increasingly referred for specialty care to tertiary centers, particularly for advice regarding initiation and monitoring of immunomodulatory therapies. However, the generalist must still be able to apply appropriate skills and technology to diagnose the disease and its complications, provide basic counseling of patients, and be aware of potential treatment options at the time of diagnosis and when therapeutic regimens fail. A general approach, supported by evidence where possible, to common and contemporary clinical issues in MS care is provided in a case-based narrative.

Adjuvants, Immunologic↗
PubMed2002

Randomized controlled trials to assess therapies for multiple sclerosis.

MS poses formidable challenges to clinical investigators. Obstacles to the study of MS therapies include disease chronicity, an unpredictable clinical course, radiologic and pathologic heterogeneity, and limited understanding of the underlying pathophysiology. Randomized controlled trials (RCTs) provide a means to assess therapeutic efficacy while reducing the risks of study bias and confounding factors that influence interpretation of results. RCTs have demonstrated that type 1 interferons and glatiramer acetate alter the short-term natural history of MS and have served as the basis of approval for the marketing of these treatments. Improvements and optimization of trial methodology may hasten the discovery of effective therapies and facilitate better comparisons of the results of individual drug trials. The most urgent need is for improved surrogate end points for clinical outcome with predictive validity for long-term disability. Even if RCT methodology is optimal, however, several limitations inherent to MS trials threaten to impede further progress, including obstacles to long-term studies (e.g., costs), patient withdrawal, and escalating sample size requirements to detect partial therapeutic benefit. There is a crucial need to develop alternative investigative methods, possibly through enhanced collaboration across centers and with industry, and by exploring innovative techniques to use existing RCT and natural history databases to greater advantage.

Glatiramer Acetate↗
PubMedDate not supplied

A serum autoantibody marker of neuromyelitis optica: distinction from multiple sclerosis.

BACKGROUND: Neuromyelitis optica is an inflammatory demyelinating disease with generally poor prognosis that selectively targets optic nerves and spinal cord. It is commonly misdiagnosed as multiple sclerosis. Neither disease has a distinguishing biomarker, but optimum treatments differ. The relation of neuromyelitis optica to optic-spinal multiple sclerosis in Asia is uncertain. We assessed the capacity of a putative marker for neuromyelitis optica (NMO-IgG) to distinguish neuromyelitis optica and related disorders from multiple sclerosis. METHODS: Indirect immunofluorescence with a composite substrate of mouse tissues identified a distinctive NMO-IgG staining pattern, which we characterised further by dual immunostaining. We tested masked serum samples from 102 North American patients with neuromyelitis optica or with syndromes that suggest high risk of the disorder, and 12 Japanese patients with optic-spinal multiple sclerosis. Control patients had multiple sclerosis, other myelopathies, optic neuropathies, and miscellaneous disorders. We also established clinical diagnoses for 14 patients incidentally shown to have NMO-IgG among 85000 tested for suspected paraneoplastic autoimmunity. FINDINGS: NMO-IgG outlines CNS microvessels, pia, subpia, and Virchow-Robin space. It partly colocalises with laminin. Sensitivity and specificity were 73% (95% CI 60-86) and 91% (79-100) for neuromyelitis optica and 58% (30-86) and 100% (66-100) for optic-spinal multiple sclerosis. NMO-IgG was detected in half of patients with high-risk syndromes. Of 14 seropositive cases identified incidentally, 12 had neuromyelitis optica or a high-risk syndrome for the disease. INTERPRETATION: NMO-IgG is a specific marker autoantibody of neuromyelitis optica and binds at or near the blood-brain barrier. It distinguishes neuromyelitis optica from multiple sclerosis. Asian optic-spinal multiple sclerosis seems to be the same as neuromyelitis optica.

Adult↗