Multiple sclerosis and childhood infections.

There is evidence that some event in childhood may determine risk of multiple sclerosis: Elevated titers to measles and other childhood infections suggest a childhood infection. Therefore, childhood infections reported by 30 patients with multiple sclerosis and matched controls were compared. Patients reported a childhood infection between 5 and 9 years (not simply exposure to an infection) more often than controls. The mean age of measles peaked somewhat later (age 7) in patients than in controls (age 4); this differnce approached statistical significance (p less than 0.1). Evidence that host response to measles is age-dependent was reviewed. It was proposed that age of measles (rather than the fact of injection) may influence the risk of developing multiple sclerosis.

Serological studies on the etiological role of measles-like virus in subacute sclerosing panencephalitis.

Significantly higher CSF titers of hemagglutination (HI) measles virus antibody were found in 22 patients with subacute sclerosing panencephalitis (SSPE) and more elevated titers of measles virus neutralization (NV) antibody were encountered in 19 patients with SSPE than in 50 children and young adults with other neurological diseases. Similar differences occurred in the sera of patients and controls. The serum: CSF antibody ratio was examined in 15 SSPE cases. All but one patient showed reduced antibody ratio (less than 80) as compared with the normal index. In addition, serological studies in some SSPE patients showed the presence of CSF antimeasles fluorescent (FA) and mixed hemadsorption (HAd) antibodies as well as serum anti-ribonucleoprotein antibody (RNP), HAd and FA had titers from 1:16 to 1:32000. SSPE patients harbored serum antibodies against three components of the measles virus as measles patients did. Most of SSPE patients had increasing CSF and serum titers of measles-like virus antibodies over the course of the disease.

Measles virus infection and multiple sclerosis: serological studies.

In 159 patients out of 161 with multiple sclerosis (MS), a significant rise in the level of measles hemagglutination inhibition (HI) antibody was found in the serum and in 92 MS patients the occurrence of measles HI antibody in the CSF was significantly more frequent. MS patients showed CSF humoral response against measles virus by neutralizing test (NV) (76%) more often than by hemagglutination test (37%). CSF FA antibody was found in 60%. In the serum of MS patients the presence of NV, HAd, FA, and GP-RNP was observed. 87% of MS patients showed lowered serum: CSF NV or HI antibody ratios and 78% had a diminished FA antibody ratio. Longitudinal study of serum HI measles virus antibody showed no substantial changes over longer period of the disease. Higher CSF measles antibody titer was found in more disabled patients with a malignant course of the disease (P less than 0.001). It is concluded that either persistent infection with proviruses or nonspecific stimulation of certain clones in individuals with genetic susceptibility provides for an excessive synthesis of humoral viral antibodies in MS.

Elevated parainfluenza virus type 1 antibody in patients with subacute sclerosing panencephalitis.

Parainfluenza virus hemagglutination inhibition (HI) antibodies were determined 3 times in the sera of 9 patients with subacute sclerosiing panencephalitis (SSPE) and 20 healthy controls matched for age and place of residence. Serum antibody against parainfluenza virus type 1 was significantly elevated in SSPE patients as compared with controls, whereas antibodies against type 2 and 3 were found to be in normal ranges. Higher titres of parainfluenza virus type 1 antibody might depend on: (1) dual viral infection, (2) cross-reaction between antigens of SSPE virus and parainfluenza virus type 1, and (3) non-specific activation of latent virus type 1 genome. The latter explanation seems to be particularly interesting since the parainfluenza type 1 antibody titres remained constant despite the clinical progression. This finding is comparable to the elevated titres against Epstein-Barr virus of adenovirus which have been found occasionally in this disease.

A case of multiple sclerosis associated with defective neuromuscular transmission.

A 38-year-old woman developed relapsing disseminated sclerosis associated with myasthenic syndrome. The cerebrospinal fluid showed 12 lymphocytes per 1 mul and paretic colloidal curve. The serum contained antibody against smooth muscle antigen (titre 1 : 10) but no antibody against nuclear antigen or VDRL antigen. Repetitive stimulation of the right ulnar nerve at 35 c/sec. demonstrated typical decrements between 70 and 72%. The prostigmine test showed significant diminishing of decrements. The possible immunopathological mechanism of myasthenic syndrome in multiple sclerosis was briefly discussed.

[The risk of multiple sclerosis development in patients with idiopathic optic neuritis: prognosis and other problems]. / Zagrozenie stwardnieniem rozsianym wsród chorych z samoistnym zapaleniem nerwu wzrokowego: zagadnienia rokownicze i inne.

The percentage of patients with idiopathic optic neuritis (ION) developing multiple sclerosis (MS) was higher in young females who had recurrent ION, especially during 4 years since the first inflammatory attack. Clinical features of ION had no prognostic value. Patients with ION developed also more frequently MS if paraclinical findings showed the occurrence of DR2, DR3, DQw1 and/or DPw4, increased CSF IgG index, CSF oligoclonal IgG, asymptomatic lesions in NMR brain images, and subclinical abnormalities in visual, brainstem auditory, somatosensory evoked potentials. The author discusses the problem whether high risk patients with ION should be given antiviral and immunomodulatory drugs which could prevent or delay the clinical onset of MS.

[Micropsia in multiple sclerosis]. / Mikropsja w stwardieniu rozsianym.

Micropsia is described in a case of remitting multiple sclerosis with left optic neuritis and spastic paraparesis. The damage to small axons in the optic nerve conducting spatial impulses from temporal and lower segments of retina might be responsible for the occurrence of transient micropsia.

[Multiple sclerosis in the year 2000: advances in the treatment with interferon beta-1b]. / Stwardnienie rozsiane w roku 2000: postepy w leczeniu interferonem beta-1b.

The decline of millennium brings forward new challenges in therapeutic immunomodulation of relapsing-remittent multiple sclerosis (RR MS). Interferon beta-1b (Betaferon) belongs to expanding family of soluble cytokines which are capable to modify beneficially cellular immunity in RR MS. IFN beta-1b is indicated for young or middle-aged, ambulant patients with RR MS who have frequent relapses, "aggressive" brain lesions in magnetic resonance imaging and higher levels of pro-inflammatory cytokines. Betaferon reduced in people with RR MS mean annual rate and severity of relapses (34% and 49%) and lengthened median time to second relapse (to 295 days). IFN beta-1b also increased the number of relapse-free patients (31%). Although the drug diminishes weakly progression and activity (disability) it might improve slightly participation (handicap) and quality of life. The course of treatment, withdrawals from the trials, side-effects and the occurrence of neutralizing antibodies to IFN beta-1b are concisely described. Combination of IFN beta-1b with other immunotherapeutic drugs needs further clinical trials.

[Therapeutic potential of interferon beta-1b and related drugs in multiple sclerosis: comparative meta-analysis]. / Terapeutyczny potencjal interferonu beta-1b i pokrewnych leków w stwardnieniu rozsianym: porównawcza meta-analiza.

The objective of this current meta-analysis is to determine whether IFN beta-1b is substantially better than other immunomodulating, immunosuppressive or anti-inflammatory drugs in modifying the clinical course of relapsing-remitting and secondary progressive multiple sclerosis (RR MS, SP MS). A comparison shows that in 2-year treatment IFN beta-1b, beta-1a s.c., glatiramer acetate, immunoglobulin G i.v. and mitoxantrone i.v. reduced annual relapse rate (45%), increased the proportion of relapse-free patients (34%), decreased the mean level of disability (-0.23 in EDSS) and diminished the fraction of RR MS patients with sustained progression (25%); p < or = 0.05. Azathioprine demonstrated considerable delay in the onset of action and loss of efficacy in the third year of treatment. IFN beta-1b and cyclical pulses of intravenous high dose methylprednisolone decreased the annual relapse rate and slowed the progression in SP MS patients; p < or = 0.04. All drugs significantly reduced the number of new and enlarging brain lesions on GdT1 and PD/T2 images in MRI (mean -68%). Furthermore, IFN beta-1b s.c. and beta-1a s.c. evidently reversed burden of the disease (BOD) on T2 images (median -4.7%); p = 0.001. However, glatiramer acetate, immunoglobulin G i.v., IFN beta-1a i.m., methylprednisolone i.m. and possibly azathiopirine failed to diminish BOD on T2 images; p = ns. It is concluded that in most RR MS patients IFN beta-1b has similar clinical effect to other immunomodulating drugs and mitoxantrone.

[Symptomatology of infrequent visual disturbances in multiple sclerosis patients]. / Symptomatologia rzadszych zaburzen wzrokowych u chorych na stwardnienie rozsiane.

Two cases of clinically certain multiple sclerosis were observed in whom rather infrequently occurring symptoms of damage to the visual pathways were noted. In one case during right-sided optic neuritis cyanopsia developed, followed after five months by left-sided alternatively darkening and lightening of vision. In another case with bilateral retrobulbar optic neuritis attacks of fading-out vision appeared when the patient fixed an object. Two years later the patient had episodes of chloropsia.

[Nuchal-paretic sign in multiple sclerosis]. / Objaw karkowo-porazny w stwardnieniu rozsianym.

A 43-year-old patient with clinically established diagnosis of multiple sclerosis had the nuchal-paretic sign. Neck flexion caused reversible deterioration of gait and increased the weakness of the right lower extremity. Although the sign is not pathognomonic for multiple sclerosis it is a peculiar pyramidal sign suggesting demyelination especially in the cervical part of the spine. Mechanical stretching of the demyelination plaques in the cervical spine reduces probably the density of the action current generated at the nodes of the demyelinated fibres.

[Dantrium in the treatment of increased muscle tonus in patients with multiple sclerosis]. / Dantrium w leczeniu wzmozonego napiecia miesniowego u chorych na stwardnienie rozsiane

In 19 patients with multiple sclerosis and 1 with subacute sclerosing panencephalitis the mean increase in muscle tonus was found to be 3.1 (range 1--4 according to Burke-Ashwort). In 10 controls with multiple sclerosis the mean spasticity was 2.4. Dantrium was given in doses up to 800 mg for 14--16 days and it caused a greater reduction of spasticity than placebo (p less than 0.05). In 12 patients (60%) varying degrees of muscle tonus reduction was observed. In 11 patients the efect of Dantrium was compared with that of other drugs (Clonazepam, Tetradiazepam, Carisoprodol and Lyoresal). In 6 cases Dantrium was a more effective drug than other muscle relaxants and in 5 cases no difference was observed or other drugs were superior to Dantrium.

[Multiple sclerosis mortality in Poland]. / Smiertelnosc na stwardnienie rozsiane w Polsce.

The total annual number of deaths among multiple sclerosis patients in Poland had been dropping gradually from 561 to 452 in the period 1969-1973, then it remained at a relatively stable level (507-528) in the years 1977-1980. The mean annual not age-adjusted mortality indices decreased from 1.72 to 1.34 and became stabilized at the levels 1.45-1.47 per 100 thousand population. The sex-adjusted mortality indices showed also an initial drop followed by a plateau. The mean life span of men with multiple sclerosis decreased slightly from 53.4 and in women from 52.7 to 50.4 years in both sexes in 1980. The author discusses the fluctuation of mortality indices and changes in the life span of patients with multiple sclerosis in Poland.

[Dyslexia of digits and numbers in multiple sclerosis]. / Aleksja cyfr i liczb w stwardnieniu rozsianym.

In a 32-year-old man with remitting-progressive multiple sclerosis a right-side hemiparesis and alexia of digits of numbers developed during an exacerbation. While reading aloud the patient changed digits, left them out or transposed. No changes were observed in reading of letters, words and no agraphia was present. Alexia persisted for about one month. The location of alexia in the occipital lobe and its association pathways with the left parietal lobe are discussed.

[Lipid peroxides in the sera of patients with multiple sclerosis]. / Nadtlenki lipidów w surowicy chorych na stwardnienie rozsiane.

Serum lipid peroxides (LPX) were determined in 24 patients with multiple sclerosis and in 30 healthy controls. Patients with relapses or chronic progression had significantly higher serum LPX level than healthy controls: mean 3.09 +/- 0.15 nmol/ml versus 2.30 nmol/ml, p less than 0.01. Relapsing-remitting patients showed slightly higher LPX level than slowly progressive patients. It is supposed that lipid peroxides are unspecific mediators of the inflammatory reaction in multiple sclerosis.

[Haptoglobin levels in the serum and the cerebrospinal fluid patients with multiple sclerosis]. / Poziom haptoglobiny w surowicy krwi i w plynie mózgowo-rdzeniowym u chorych na stwardnienie rozsiane.

In 47 patients with multiple sclerosis and 10 with other diseases of the nervous system determinations of haptoglobin were performed in the serum and cerebrospinal fluid by the method of Owen et al. The Hp level in the serum of multiple sclerosis patients was normal. Its level in the cerebrospinal fluid was higher in multiple sclerosis patients than in cases of other nervous system diseases (statistically significant difference, p less than 0.001). Raised value of the Hp/IgG index in the cerebrospinal fluid of multiple sclerosis patients points to increased permeability of the blood-brain barrier. The so called normal Hp/IgG index was found in multiple sclerosis patients with high Hp and IgG level. Low Hp/IgG index suggested the possibility of IgG synthesis in the brain of patients with this disease. The comparison of the protein level and protein indexes showed that raised IgG level in the cerebrospinal fluid was present in 80% of multiple sclerosis cases, raised Kabat index in 50%, and low Hp/IgG index in 48%.

[Oscillopsia in multiple sclerosis]. / Oscylopsia w stwardnieniu rozsianym.

In a 20-year-old woman one of the presenting signs of multiple sclerosis was recurrent oscillopsia. Fixation of eyes while reading released during upward and downward gaze oscillopsia with variable amplitude and frequency. Electronystagmographic investigation failed to reveal signs of damage to the vestibular organ or vestibulo-oculomotor pathways. The most likely explantation of oscillopsie was, in this case, lesion of the pathway connecting the cerebellum with oculumotor nerve nuclei.

[Connection between severe perivenous retinitis with retinovitreal hemorrhage and disseminated sclerosis]. / Powiazanie ciezkiej postaci okolozylnego zapalenia siatkówki i krwotoku do szklistki i siatrówki ze stwardnieniem rozsianym

In a 49-year-old man with temporal pallor of the left optic nerve papilla and increasing spastic paraparesis and with slight lymphocytosis in the cerebrospinal fluid perivenous retinitis was diagnosed. The peripheral retinal veins were covered with characteristic white sheaths, focal formation of new blood vessels, retinal microscopic haemorrhages and residues after vitreal haemorrhage were found. The authors discuss the possibility of a connection between disseminated sclerosis and perivenous retinitis and their possible common aetiology.

[Cerebrospinal fluid prostaglandins in multiple sclerosis. Preliminary report]. / Prostaglandyny w plynie mózgowo-rdzeniowym u chorych na stwardnienie rozsiane. Doniesienie wstepne.

In 14 patients with multiple sclerosis exacerbations, in 7 with slowly progressive or stationary disease, and 5 patients with intervertebral disc prolapse the levels of total prostaglandins (PGs) were determined in the cerebrospinal fluid. The determinations were done by bioassay according to Ferreira and Vane. In multiple sclerosis patients the level of total PGs was significantly higher in the cerebrospinal fluid (286 +/- 20.3 pg/ml) than in patients with disc prolapse (142 +/- 7.7 pg/ml) (p less than 0.01). This rise in this level might be due to increased synthesis of PGs by activated macrophages, lymphocytes and neutrophils or to increased hypothalamic response to stress.

[Gamma globulin subfractions and immunoglobulin G in the cerebrospinal fluid of patients with multiple sclerosis, subacute sclerosing panencephalitis and other diseases of the nervous system]. / Podfrakcja gamma-globulin i immunoglobulina G w plynie mózgowo-rdzeniowym chorych na stwardnienie rozsiane, podostre stwardniajace zapalenie mózgu i inne choroby ukladu nerwowego.

CSF samples were obtained from 22 patients with multiple sclerosis, 14 patients with subacute sclerosis panencephalitis, and 10 with neuroses or headaches. Most samples were investigated simultaneously by a sensitive method of electrophoresis in polyacrylamide gel (PE) and radial immunodiffusion (RID). The absolute IgG concentration was in multiple sclerosis 6.8 +/- 3.3 mg/100 ml, and in SSPE 21.4 +/- 16.8 mg/100 ml and it was higher than in control subjects (p less than 0.01). In 84% of MS patients the Bauer index (IgG: total protein) was raised, 72% had relatively raised subfractions gamma 2-gamma 3 in PE, 64% had higher absolute concentration of GG (0.045 g/l or more) and 63% had increased proportion of one of gammaglobulin subfractions (over 4%). Of positive diagnostic importance was a rise of the IgG: total protein index, since 7 patients with SM (31%) with normal per cent gammaglobulin level (less than or equal to 13%) had an evident rise of this index. Raised value of the index IgG: total protein (greater than or equal to 10%) was observed also in 100% of SSPE cases, while in 92% the proportional value of one of gamma globulin subfractions was increased (over 4%), in 92% the subfractions gamma 3-gamma 4 were increased, in 85-86% of patients the relative (over 13%) and absolute (0.045 g/l or more) levels of gammaglobulins were increased. The index beta/gamma in MS and SSPE was 0.85 and 0.57 respectively, and was significantly lower than in patients with headaches. The authors discuss the diagnostic value of these findings.