Cine cerebrospinal fluid imaging in multiple sclerosis.

PURPOSE: To investigate cerebrospinal fluid (CSF) dynamics in the aqueduct of Sylvius in multiple sclerosis (MS) patients and healthy controls (HC) using cine phase contrast imaging. MATERIALS AND METHODS: In all, 67 MS patients (48 relapsing-remitting [RR] and 19 secondary-progressive [SP]), nine patients with clinically isolated syndrome (CIS), and 35 age- and sex-matched HC were examined. CSF flow and velocity measures were quantified using a semiautomated method and compared with clinical and magnetic resonance imaging (MRI) disease outcomes. RESULTS: Significantly decreased CSF net flow was detected in MS patients compared to HC (-3.7 vs. -7.1 µL/beat, P = 0.005). There was a trend for increased net positive flow between SP, RR, and CIS patients. Altered CSF flow and velocity measures were associated with more severe T1 and T2 lesion volumes, lateral and fourth ventricular volumes, and third ventricular width in MS and CIS patients (P < 0.01 for all). In CIS patients, conversion to clinically definite MS in the following year was related to decreased CSF net flow (P = 0.007). There was a trend between increased annual relapse rate and altered CSF flow/velocity measures in RRMS patients (P < 0.05). CONCLUSION: CSF flow dynamics are altered in MS patients. More severe clinical and MRI outcomes in RRMS and CIS patients relate to altered CSF flow and velocity measures.

Acute demyelinating lesions with restricted diffusion in multiple sclerosis.

BACKGROUND AND OBJECTIVES: It is widely accepted that typical acute demyelinating lesions in relapsing-remitting multiple sclerosis (RRMS) exhibit vasogenic edema with increased diffusion, as demonstrated by an increased apparent diffusion coefficient on MRI. In contrast, acute ischemic lesions demonstrate cytotoxic edema with restricted diffusion. Recent reports have documented selected cases of acute demyelinating lesions exhibiting restricted diffusion (ADLRD) in MS. We aimed to assess the morphologies, distributions, signal characteristics and changes over time of nine ADLRD. An additional goal was to obtain clinical correlations and relate our findings to all previously published case reports describing ADLRD. METHODS: A retrospective case series study was performed at two academic centers. MRI characteristics of nine ADLRD found in six RRMS patients were compared with typical active symptomatic contrast-enhancing lesions with increased or normal diffusion in control RRMS patients. RESULTS: The average size of ADLRD was not significantly different from typical lesions. A periventricular location and faint signal on T2-weighted images were significantly more common for ADLRD compared with typical lesions. Two patients with ADLRD on initial MRI exhibited new ADLRD on their follow up scans. CONCLUSION: Our results and review of prior published cases suggest that ADLRD represent a new variant of MS lesion. The restricted diffusion that is a characteristic of ADLRD on MRI is a new challenge in the differential diagnosis of stroke in young adults. The pathogenesis of ADLRD remains to be understood.

Gerstmann-Sträussler-Scheinker syndrome masquerading as multiple sclerosis.

Gerstmann-Sträussler-Scheinker syndrome (GSS) is a rare degenerative disorder of the central nervous system that belongs to the family of human spongiform encephalopathies, or prion diseases. GSS is almost always inherited and mostly carried in an autosomal dominant pattern. Nevertheless, GSS is genetically and phenotypically heterogeneous; among the different prion diseases GSS has the longest clinical course thereby has the potential to mimic the clinical course of different neurological disorders. Here, we report of a patient with a progressive ataxic syndrome, with MRI and CSF findings suggestive of a demyelinating-inflammatory process as multiple sclerosis and the cues that prompted to a final diagnosis of GSS.

A randomized, blinded, parallel-group, pilot trial of mycophenolate mofetil (CellCept) compared with interferon beta-1a (Avonex) in patients with relapsing-remitting multiple sclerosis.

BACKGROUND: Mycophenolate mofetil (MMF, CellCept®) has been utilized as an antirejection agent in transplant recipients and in patients with myriad autoimmune disorders including multiple sclerosis (MS). OBJECTIVE: To investigate radiographic and clinical safety involving monotherapy use of daily oral MMF (1 g b.i.d.) versus weekly intramuscular interferon beta 1a (Avonex® at 30 mcg) in relapsing-remitting MS (RRMS). METHODS: We organized a randomized, serial, 6-monthly, MRI-blinded, parallel-group multicenter pilot study to determine the safety of MMF versus interferon beta monotherapy in 35 untreated patients with RRMS, all of whom exhibited evidence of gadolinium (Gd) enhancement on a screening MRI of the brain. The primary outcome was the reduction in the cumulative mean number of combined active lesions (CAL), new Gd-enhancing lesions, and new T2 lesions on MRI analyses. RESULTS: Both interferon beta and MMF appeared safe and well tolerated in the majority of patients. There was no difference between MMF therapy and the standard regimen of interferon beta therapy on the primary safety MRI endpoints of the study. However, the MMF group showed a trend toward a lower accumulation of combined active lesions, CAL, Gd and T2 lesions when compared with interferon beta treated patients. CONCLUSIONS: The results from this pilot study suggest that the application of MMF monotherapy in MS deserves further exploration.

Progressive tumefactive inflammatory central nervous system demyelinating disease in an acquired immunodeficiency syndrome patient treated with highly active antiretroviral therapy.

We report here a case of progressive tumefactive inflammatory central nervous system (CNS) demyelinating disease in a human immunodeficiency virus (HIV)-seropositive patient treated with highly active antiretroviral therapy (HAART). Biopsy revealed diffuse macrophage and perivascular T-lymphocytic infiltrates with severe demyelination and relative axonal sparing. The disease progressed in a centrifugal fashion, to involve bihemispheric cerebral white matter, with subsequent central necrotic changes and atrophy. Treatment with HAART was discontinued, and inflammatory disease was treated with subcutaneous interferon (IFN)beta-1a. Massive brain edema was controlled with courses of intravenous corticosteroids. Following fulminant monophasic disease, the patient stabilized with no evidence of disease progression over long-term follow up. We propose that immune response reconstituted by HAART can unmask an autoimmune response in susceptible individuals, analogous to the enhanced immune response to the preexisting acquired immunodeficiency syndrome (AIDS) opportunistic infections. Therapeutic options are considered.

Acute disseminated encephalomyelitis after liver transplantation.

BACKGROUND: During the past 10 years, acute disseminated encephalomyelitis has been reported a few times after organ transplantation. OBJECTIVE: To report a case of acute disseminated encephalomyelitis as a complication of liver transplantation. DESIGN: Case report. SETTING: The University of North Carolina Hospital and Medical Center, Chapel Hill. Patient A 49-year-old woman admitted because of acute onset of paresthesias, sensory loss, and weakness after liver transplantation. Acute clinical presentation, results of imaging studies, and comprehensive laboratory evaluation were consistent with acute disseminated encephalomyelitis. INTERVENTIONS: High-dose intravenous corticosteroid therapy followed by maintenance oral dosing. MAIN OUTCOME MEASURES: Clinical and magnetic resonance imaging improvement. RESULTS: Corticosteroid therapy halted clinical progression, with partial resolution of lesions on magnetic resonance images of the brain and spinal cord. CONCLUSIONS: This is, to our knowledge, the first report of acute disseminated encephalomyelitis after liver transplantation. Possible pathogenic mechanisms include a cross-reactive immune response to foreign antigens present within the transplanted organ, or an inflammatory response triggered by viral infection in an immunocompromised host.

Changes in gray-/white-matter ratios in the parahippocampal gyri of late-onset schizophrenia patients.

OBJECTIVE: Recent neuropathological studies have reported that late-onset schizophrenia patients exhibit a restricted limbic tauopathy, glial tangles (thorn-shaped astrocytes), scarce amyloid deposition, and preservation of hippocampal pyramidal cells. The present article is an attempt at finding a macroscopic correlate to the described pathology. METHODS: A group of 13 normal-onset (<40 years) schizophrenic patients, 13 late-onset (>40 years) schizophrenia patients, and 8 comparison clients were studied, based on fulfillment of diagnostic criteria (e.g., DSM-III) and availability of suitable tissue. A computerized image analysis provided areal measurements of the hippocampal formation. Both hemispheres and two levels (mammillary bodies and lateral geniculate nucleus) were studied. In order to avoid corrections based on tissue shrinkage, results were expressed as ratios (e.g., parahippocampal gray/white matter). RESULTS: Late-onset schizophrenic patients exhibit significant alterations in the gray-/white-matter ratio of the parahippocampal gyrus, affecting both hemispheres and all levels examined. This finding can best be explained by the preservation of gray matter and concomitant reduction of white matter in affected parahippocampal gyri. CONCLUSION: The presence of neuritic changes, preservation of pyramidal cell numbers, and of areal diminution of the parahippocampal white matter can best be explained by a dying-back neuropathy.