William A. Sibley

Recommended diagnostic criteria for multiple sclerosis: Guidelines from the International Panel on the Diagnosis of Multiple Sclerosis

The International Panel on MS Diagnosis presents revised diagnostic criteria for multiple sclerosis (MS). The focus remains on the objective demonstration of dissemination of lesions in both time and space. Magnetic resonance imaging is integrated with clinical and other paraclinical diagnostic methods. The revised criteria facilitate the diagnosis of MS in patients with a variety of presentations, including “monosymptomatic” disease suggestive of MS, disease with a typical relapsing‐remitting course, and disease with insidious progression, without clear attacks and remissions. Previously used terms such as “clinically definite” and “probable MS” are no longer recommended. The outcome of a diagnostic evaluation is either MS, “possible MS” (for those at risk for MS, but for whom diagnostic evaluation is equivocal), or “not MS.”

Longitudinal analyses of the effects of neutralizing antibodies on interferon beta-1b in relapsing-remitting multiple sclerosis

We have analysed data on exacerbation rates, Expanded Disability Status Scale (EDSS) scores, and lesion burdens using the results of two neutralizing antibody (NA B) assays (C PE and MxA) from the pivotal relapsing-remitting multiple sclerosis (MS) trial of interferon beta-1b (IFNB) with a longitudinal appro ach, where the influence of NA Bs in individual patients is assessed by comparing responses during NAB- positive and NA B-negative periods. There are apparent influences on exacerbation rate related to dose of IFNB, titer level, and duration of positivity. With the MxA assay, exacerbation rates after switching to NA B-positive status are estimated to be 28% higher [95% confidence interval (CI): (-15%, 92%)] and -2% higher [95% CI: (-21%, 21%)] on the low- and high-dose IFNB arms, respectively. When compared with all NA B-negative periods, exacerbation rates during NA B-positive periods are estimated to be 29% higher [95% C I: (0%, 67%)] and 18% higher [95% CI: (0%, 40%)] on the low- and high-dose IFNB arms, respectively. When NA B-positive patients again become NA B-negative, no evidence of increased exacerbation rates could then be demonstrated. More detailed exploratory analyses indicate that the effects are most evident in the approximately 20% of patients developing high titers. In these patients, the influence of NABs may be self-limited, as titers often diminish or NA Bs become undetectable with time.

Seasonal variation of multiple sclerosis exacerbations in Arizona

We studied 178 MS patients and 82 controls for 5 years. A monthly pattern in the frequency of exacerbations in Arizona differed from the patterns seen in other regions of the world. Exacerbations were most common in warmer months. No explanation for this was found. In this prospective study, the frequency of viral infections in the MS patients was lower than in the controls.

A prospective study of physical trauma and multiple sclerosis.

During an eight year period 170 multiple sclerosis (MS) patients and 134 controls without physical impairment were followed closely to record all episodes of physical trauma and to measure their effect on exacerbation rate and progression of MS. There was a total of 1407 instances of trauma, which were sorted into various categories. Overall there was no significant correlation between all-traumas and disease activity. There was, however, a statistically significant negative correlation between traumatic episodes and exacerbations in 95 patients who had exacerbations during the programme, due primarily to less activity of the disease during a three month period following surgical procedures and fractures. Electrical injury had a significant positive association with exacerbation using a three month at-risk period, but there were no other significant positive correlations in any other category of trauma, including minor head injuries; there were no cases of head injury with prolonged unconsciousness. There was no linkage between the frequency of trauma and progression of disability. MS patients had two to three times more trauma than controls.

Uveitis, perivenous sheathing and multiple sclerosis.

Pars planitis (peripheral uveitis) and perivenous sheathing are two ocular phenomena associated with multiple sclerosis (MS). A total of 163 ocular examinations were performed on 127 MS patients at the university of Arizona Health Sciences Center. The prevalence of pars planitis in our study is lower (2.4 percent) than found by others, but significantly higher than its occurrence in the general population. We attribute our lower prevalence to the method of ocular examination (scleral depression and indirect ophthalmoscopy), as well as to firmly defined criteria necessary to make the diagnosis of pars planitis. The incidence of perivenous sheathing (11 percent) reported by us is consistent with the experience of others; however, this finding was noted more frequently in patients with the progressive form of MS. No perivenous sheathing was found to develop within the first few weeks following 31 exacerbations, and no association was identified between its presence and the severity of neurologic disability.

Trauma as an etiologic and aggravating factor in multiple sclerosis

We carried out a retrospective and prospective epidemiologic study designed to detect an association between trauma and multiple sclerosis in 130 patients and 82 age- and sex-matched controls. Electrical injury was followed by an increased frequency of exacerbation, which did not achieve statistical significance. There was no statistically significant association between other types of trauma and onset or deterioration of the disease. These findings do not prove that such an association cannot exist for any one individual patient; however, they do not provide evidence to support this idea.

Cerebral infarction immediately after ingestion of hydrogen peroxide solution.

Background We report the clinical and neuroimaging findings of a patient who sustained multiple cerebral infarcts after the ingestion of concentrated hydrogen peroxide solution sold as a “health food” product. Case Description An 84-year-old man sustained focal neurological deficits immediately after ingesting 30 mL of 35% hydrogen peroxide solution. Physical examination disclosed a left hemiparesis, frontal release signs, and cerebellar dysfunctions. Magnetic resonance imaging revealed multiple cerebral and cerebellar infarctions in the anterior, middle, and posterior vascular territories. Conclusions The likely mechanism of pathogenesis involves cerebral oxygen gas embolization. The use of hyperbaric therapy should be considered in treating hydrogen peroxide poisoning.

Neurologic Manifestations of Thrombotic Thrombocytopenic Purpura

NUMEROUS individual case reports and reviews1.2 on thrombotic thrombocytopenic purpura adequately describing the clinical manifestations and pathologic findings have appeared in recent years. Nevertheless, thrombotic thrombocytopenic purpura is a rare disease, since only about 100 cases have been reported. Therefore, it is relatively unfamiliar to many neurologists. Since patients with this disease are often seen by the neurologist, either initially or in consultation, because of the prominence of neurologic manifestations, we b v e considered it advisable to review a s e r s e s o f l l ~ ~ . at the CdumbiaPresbyterian Medical Center. Moschowitz3 in 1925 first described the pathologic findin s in one case which manifested many of & e clinical findings that are now associated with this illness. He termed it “an acute febrile pleiochromic anemia with hyaline thrombosis of the terminal arterioles and capillaries.” With the addition of other cases to the literature, there has been an evolution of a rather typical clinical icture and

The case for rhinoviruses in the pathogenesis of multiple sclerosis

The family Picornaviridae includes six genera: rhinoviruses, enteroviruses including polioviruses, apthoviruses, cardioviruses, hepatoviruses, and parechoviruses. Rhinoviruses are probably the most common microbe affecting humans, responsible for many or most cases of the ‘common cold’ or upper respiratory infection (URI). We present evidence for the hypothesis that there may be an important link between rhinovirus infections and the induction of multiple sclerosis (MS). These arguments are presented as a basis for thought, discussion, and further research in this important field. At least five observations lend support to the possibility that rhinoviruses may be implicated in MS:

PHYSICAL TRAUMA AND MULTIPLE SCLEROSIS

There is a normal human tendency to blame illness on antecedent events, whether the latter be psychological stresses, physical traumas, infections, or changes in medication or the weather. Nowhere is this tendency more common than in multiple sclerosis (MS), where exacerbations occur unpredictably and at odd intervals. Recent serial MRI studies reveal t h a t worsening in MS (new o r enlarging lesions) occurs much more often than previously suspected. Willoughby et a1 found that, in early MS, two to three new lesions per year were the average,’ and in secondary chronic progressive MS, even more activity is seen: four to six new lesions or enlargement of old lesions each year.2 Although such studies might be interpreted as indicating that MS has a life of its own, one cannot easily dismiss the possibility of an environmental influence. These serial MRI studies quote mean frequencies of new activity. Some patients have stable MRIs for extended periods only t o finally have another acute relapse of symptoms, usually associated with an appropriate change in MR findings. Nor can genetic factors entirely account for MS; the highest concordance rate in identical twins is approximately 40%, again suggesting that external influences may play a role. All experienced neurologists have seen attacks with a close temporal relationship to an infection, an episode of physical trauma, or a period of emotional stress. Augustus D’Este, a grandson of George 111, whose diary described his own case in the early 19th century, says that he developed the first symptoms (suggesting bilateral optic neuritis) during the funeral of a r e l a t i ~ e . ~ Laymen often say “after this, therefore because of this” (post hoc, ergo propter hoe), but this is an uncritical approach and could be used to show that a full moon or eating strawberries causes exacerbations. Striking as the temporal relationship may be in such individual cases, they do not prove that any of the most frequently cited putative environmental factors are anything more than coincidental occurrences. To prove that they are actual risk factors, one must show in a prospective way that exacerbations occur more frequently after such events than at other times. In one large prospective study, carried out over an 8-year period, patients were contacted at monthly intervals about a variety of environmental factors, including stressful life events, infections, and physical trauma. Patients were seen as soon as possible after symptoms that suggested exacerbation, and the fact of exacerbation was verified and the date of occurrence recorded. In the absence of new symptoms, patients were examined routinely every 3 month^.^-^ In this manner, the dates of exacerbations and external happenings could be correlated. I t was then possible to determine, for example, whether dental procedures had triggered exacerbation. Did more exacerbations occur in the 3-month cumulative periods after such procedures than in the same patients when not at risk (NAR) from the hypothesized risk of a dental procedure? Using this methodology, it was possible t o show that dental procedures were not a statistical risk factor-ie, that exacerbations occurred no more frequently after such procedures than they did a t other times in the study when the same patients were NAR (table 1). When there was a temporal relationship between dental trauma and subsequent exacerbation, we could not demonstrate a predilection for brainstem localization (table 2). Table 3 presents a summary of the overall results, which have been published separately e l~ewhere .~-~ By far, the strongest environmental risk factor identified was virus-like infection^.^ This relationship has been confirmed in three shorter prospective s t ~ d i e s , ~ ~ suggesting that MS is primarily a postinfectious phenomenon. Stressful life events showed only a weakly positive effect with some caveats that the positivity of the data may have been influenced by patient bias during periods when concurrent reporting of exacerbation and stress was possible5; the low rate of exacerbation in MS patients in Tel Aviv during a period of missile bombardment supports the idea that emotional stress is not a major precipitant of new episodes of MS.l0 Physical trauma was not a risk factor in our studies.6 Siva et al, at the Mayo Clinic, present important new data in this issue1‘ regarding the relationship