Progressive Necrotic Myelopathy:
Clinical Course In 9 Patients
Katz JD, Ropper AH
Arch Neurol 2000 Mar;57(3):355-61
St Elizabeth's Medical Center, Neurology Service, Boston, Mass 02135, USA
PMID# 10714661; UI# 20177143
To review the clinical, laboratory, and radiological findings of 9 patients who had Progressive Idiopathic Myelopathy with evidence of Spinal Cord Necrosis.
Design And Methods
We reviewed personally examined cases of Myelopathy that fulfilled the following criteria:
- Regional loss of reflexes, flaccidity, and muscle Atrophy
- Magnetic Resonance Imaging showing a shrunken or Cavitated Cord without evidence of AterioVenous malformation
- ElectroMyogram showing denervation over several contiguous Spinal Cord Segments with preservation of sensory potentials in some cases
- The absence of evidence of Systemic Disease or Neoplasm
The illness began in these patients after the age of 40 years, with prominent burning or tingling limb pain, occasionally with radicular features or with less well-defined back, neck, or abdominal pain.
Leg or infrequently arm weakness appeared concurrently or soon after the onset of pain. The most distinctive feature was a saltatory progression of symptoms, punctuated by both acute and subacute worsenings approximately every 3 to 9 months, culminating in Paraplegia or Tetraplegia.
The distinguishing clinical findings, together indicative of destruction of Gray Matter elements of the Cord, were limb Atrophy, persistent Areflexia, and Flaccidity.
The concentration of CerebroSpinal Fluid protein was typically elevated between 500 g/L and 1000 g/L, without OligoClonal Bands, accompanied infrequently by Pleocytosis.
Magnetic Resonance Imaging showed features suggesting Cord Necrosis, specifically swelling, T2-weighted HyperIntensity, and Gadolinium enhancement over several Spinal Cord segments, succeeded months later by Atrophy in the same regions.
Necrosis of the Cord was found in biopsy material from one patient and postmortem pathology in another case, but Inflammation and blood vessel abnormalities were absent.
Only 2 patients had prolonged Visual Evoked Responses. The disease progressed despite ImmuneModulating treatments although several patients had brief epochs of limited improvement.
The saltatory course, prolonged Visual Evoked Responses in 2 patients, and a Cranial abnormality on Magnetic Resonance Imaging in another, raised the possibility of a link to Multiple Sclerosis.
However, the normal Cranial Magnetic Resonance Imaging scans in 6 other patients, uniformly absent OligoClonal Bands, and poor response to treatment were atypical for Multiple Sclerosis.
On the basis of shared clinical and laboratory features, Idiopathic Progressive Necrotic Myelopathy is indistinguishable from a limited form of Devic Disease.
Increased Expression Of Neutral EndoPeptidase (NEP) And AminoPeptidase N (APN) On Peripheral Blood MonoNuclear Cells In Multiple Sclerosis
Ziaber J, Baj Z, Pasnik J, Chmielewski H, Tchorzewski H
Immunol Lett 2000 Feb 1;71(2):127-9
Military Medical Academy, Dept of Neurology, Lodz, Poland
PMID# 10714440; UI# 20176900
We studied CD10 Ag of Neutral EndoPeptidase (NEP) and CD13 Ag of AminoPeptidase N (APN) expression on Peripheral Blood MonoNuclear Cells (PBMC), as cells activation markers and for their TransEndothelial migration properties in three groups of MS patients (total 58);
- With Acute Exacerbation of MS (n = 18)
- Primary/Progressive MS (n = 17)
- With MS Remission (n = 23)
The control group (OND) consisted of 24 patients, suffering from Other NonInflammatory Neurological Diseases. CD10 Ag and CD13 Ag expression on PBMC was higher in clinically active MS (Acute Exacerbation and Progressive MS) compared to MS Remission and OND groups.
Our study suggests that CD10 Ag and CD13 Ag can be useful MonoNuclear Cell activation markers in the course of MS. CD13 Ag expression on PBMC may be also the sensitive marker of these cells TransEndothelial migration properties.
Effect Of ß And Anti-IFN-ß AntiBodies On NK Cells In Multiple Sclerosis
Perini P, Wadhwa M, Buttarello M, Meager A, Facchinetti A, Thorpe R, Biasi G, Gallo P
J NeuroImmunol 2000 Jun 1;105(1):91-95
Univ of Padova, Dept of Neurological and Psychiatrical Sciences, Second Neurological Clinic, via E. Vendramini 7, 35137, Padova, Italy
We analyzed longitudinally the numbers of CD3-CD16+(Natural Killer Cells, NK) and CD3-CD57+Cells (a subset of NK) in 15 IFN-ß-1b- and 12 IFN-ß-1a-treated Relapsing/Remitting Multiple Sclerosis (RRMS) patients.
IFN-ß-1b (Betaferon((R)))-treated RRMS patients showed a rapid and marked reduction in the number of both NK subsets which started 1 month after therapy initiation, and reached highest significance after 3 months (P=0.000); however, figures reverted to pre-treatment values following the appearance of Anti-IFN-ß AntiBodies.
In IFN-ß-1a (Avonex)-treated RRMS patients, the decrease in both CD3-CD16+and CD3-CD57+Cell number was slower but more persistent; anti-IFN-ß AntiBodies were only rarely detected in these patients, and at lower Titers than in IFN-ß-1b-treated ones.
Our findings suggest that NK cells might be one of the major Immunological targets of IFN-ß-based treatments.
Polymorphism Analysis Suggests That The Gelatinase B Gene Is Not A Susceptibility Factor For Multiple Sclerosis
Nelissen I, Vandenbroeck K, Fiten P, Hillert J, Olsson T, Giovanna Marrosu M, Opdenakker G
J NeuroImmunol 2000 Jun 1;105(1):58-63
Univ of Leuven, Rega Institute for Medical Research, Laboratory of Molecular Immunology, Minderbroedersstraat 10, 3000, Leuven, Belgium
The human Gelatinase B (MMP-9) Gene promoter region contains a CA microsatellite repeat and a single Nucleotide polymorphism which are known to influence transcriptional activity.
These two polymorphisms were used to investigate the existence of an association between Multiple Sclerosis (MS) susceptibility and the MMP-9 gene.
In a case-control analysis of 345 Swedish individuals and in a study of 125 Sardinian simplex families no Genetic associations between the Gelatinase B Gene polymorphisms and MS susceptibility were found.
These data reinforce the suggestion of Epistasis in the regulation of the MetalloProteinase-inhibitor balance in MS.
Cytokine-Induced Modulation Of Cellular Adhesion To Human Cerebral Endothelial Cells Is Mediated By Soluble Vascular Cell Adhesion Molecule-1
Kallmann BA, Hummel V, Lindenlaub T, Ruprecht K, Toyka KV, Rieckmann P
Brain 2000 Apr;123(Pt 4):687-697
Univ of Wurzburg, Clinical Research Unit for Multiple Sclerosis and NeuroImmunology, Germany
Tumor Necrosis Factor-alpha (TNF-) has been proposed as one of the key mediators of inflammatory diseases of the CNS such as Multiple Sclerosis.
It has been shown to induce the expression of Adhesion Molecules which is a prerequisite for the transmigration of Immune Cells through the Blood-Brain Barrier.
We therefore investigated the role of TNF- in the expression and release of Vascular Cell Adhesion Molecule-1 (VCAM-1) in cultures of Human Cerebral Endothelial Cells (HCEC).
In comparison with Peripheral Blood MonoNuclear Cells (PBMC).
A time- and dose-dependent expression of VCAM-1 and release of soluble VCAM-1 was detected in HCEC but not PBMC.
TNF--induced release of soluble VCAM-1 was further increased by cotreatment with Interferon-ß (IFN-ß), while IFN-ß alone did not affect VCAM-1 expression or the release of soluble VCAM-1.
In addition, we observed that preincubation of PBMC with soluble VCAM-1 completely blocked their adhesion to HCEC.
In conclusion, the ProInflammatory effect of TNF- on HCEC, which involves the induction of VCAM-1 expression and cellular adhesion, is followed by the consecutive effects of soluble VCAM-1 release in blocking adhesion and downregulating further cellular infiltration.
Increasing soluble VCAM-1 release during active inflammation could be another mechanism by which IFN-ß treatment exerts protective effects in Multiple Sclerosis patients.