One method of evaluating the degree of neurologic impairment in MS has been the combination of grades (0 = normal to 5 or 6 = maximal impairment) within 8 Functional Systems (FS) and an overall Disability Status Scale (DSS) that had steps from 0 (normal) to 10 (death due to MS). A new Expanded Disability Status Scale (EDSS) is presented, with each of the former steps (1,2,3 . . . 9) now divided into two (1.0, 1.5, 2.0 . . . 9.5). The lower portion is obligatorily defined by Functional System grades. The FS are Pyramidal, Cerebellar, Brain Stem, Sensory, Bowel & Bladder, Visual, Cerebral, and Other; the Sensory and Bowel & Bladder Systems have been revised. Patterns of FS and relations of FS by type and grade to the DSS are demonstrated.

https://n.neurology.org/content/neurology/33/11/1444.full.pdf

Rating neurologic impairment in multiple sclerosis An expanded disability status scale (EDSS)

Several schemes for the diagnosis and clinical classification of multiple sclerosis (MS) have been advanced [l}. The best known is that published by Schumacher et alC31. The criteria for this scheme were established in order to select patients for participation in therapeutic trials, and pertain only to what might be called definite MS. No provision was made for incorporating supportive laboratory data into the diagnostic criteria. As no reliable specific laboratory test for the diagnosis of MS has been discovered, the diagnosis remains a clinical one, and there is still a need for clinical diagnostic criteria. However, several laboratory and clinical procedures have been developed within the last decade which aid greatly in demonstrating neurological dysfunction attributable to lesions, and even the lesions themselves. One problem with the various published diagnostic classifications is their discrepant terminology: what is considered “probable” in one is called “definite” in another. Another problem is that all the proposed schemes require much subjective judgment, a difficulty which cannot be completely overcome but can be diminished by adding to the clinical evaluation the results of laboratory, neuroimaging, neuropsychological, and neurophysiological procedures. Today there is a need for more exact criteria than existed earlier in order to conduct therapeutic trials in multicenter programs, to compare epidemiological surveys, to evaluate new diagnostic procedures, and to estimate the activity of the disease process in MS. Method and Procedure

New diagnostic criteria for multiple sclerosis: guidelines for research protocols.

Objective: To improve clinical recognition and provide research diagnostic criteria for three clinical syndromes associated with frontotemporal lobar degeneration. Methods: Consensus criteria for the three prototypic syndromes-frontotemporal dementia, progressive nonfluent aphasia, and semantic dementia-were developed by members of an international workshop on frontotemporal lobar degeneration. These criteria build on earlier published clinical diagnostic guidelines for frontotemporal dementia produced by some of the workshop members. Results: The consensus criteria specify core and supportive features for each of the three prototypic clinical syndromes and provide broad inclusion and exclusion criteria for the generic entity of frontotemporal lobar degeneration. The criteria are presented in lists, and operational definitions for features are provided in the text. Conclusions: The criteria ought to provide the foundation for research work into the neuropsychology, neuropathology, genetics, molecular biology, and epidemiology of these important clinical disorders that account for a substantial proportion of cases of primary degenerative dementia occurring before the age of 65 years.

Frontotemporal lobar degeneration A consensus on clinical diagnostic criteria

Recent neuropathologic autopsy studies found that 15 to 25% of elderly demented patients have Lewy bodies (LB) in their brainstem and cortex, and in hospital series this may constitute the most common pathologic subgroup after pure Alzheimer's disease (AD). The Consortium on Dementia with Lewy bodies met to establish consensus guidelines for the clinical diagnosis of dementia with Lewy bodies (DLB) and to establish a common framework for the assessment and characterization of pathologic lesions at autopsy. The importance of accurate antemortem diagnosis of DLB includes a characteristic and often rapidly progressive clinical syndrome, a need for particular caution with neuroleptic medication, and the possibility that DLB patients may be particularly responsive to cholinesterase inhibitors. We identified progressive disabling mental impairment progressing to dementia as the central feature of DLB. Attentional impairments and disproportionate problem solving and visuospatial difficulties are often early and prominent. Fluctuation in cognitive function, persistent well-formed visual hallucinations, and spontaneous motor features of parkinsonism are core features with diagnostic significance in discriminating DLB from AD and other dementias. Appropriate clinical methods for eliciting these key symptoms are described. Brainstem or cortical LB are the only features considered essential for a pathologic diagnosis of DLB, although Lewy-related neurites, Alzheimer pathology, and spongiform change may also be seen. We identified optimal staining methods for each of these and devised a protocol for the evaluation of cortical LB frequency based on a brain sampling procedure consistent with CERAD. This allows cases to be classified into brainstem predominant, limbic (transitional), and neocortical subtypes, using a simple scoring system based on the relative distribution of semiquantitative LB counts. Alzheimer pathology is also frequently present in DLB, usually as diffuse or neuritic plaques, neocortical neurofibrillary tangles being much less common. The precise nosological relationship between DLB and AD remains uncertain, as does that between DLB and patients with Parkinson's disease who subsequently develop neuropsychiatric features. Finally, we recommend procedures for the selective sampling and storage of frozen tissue for a variety of neurochemical assays, which together with developments in molecular genetics, should assist future refinements of diagnosis and classification.

Consensus guidelines for the clinical and pathologic diagnosis of dementia with Lewy bodies (DLB) Report of the consortium on DLB international workshop

https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(05)71142-9.pdf

Acquired mutation of the tyrosine kinase JAK2 in human myeloproliferative disorders.

The worldwide distribution of multiple sclerosis (MS) can be described within three zones of frequency: high, medium, and low. The disease has a predilection for white races and for women. Migration studies show that changing residence changes MS risk. Studies of persons moving from high- to low-risk areas indicate that in the high-risk areas, MS is acquired by about age 15. Moves from low- to high-risk areas suggest that susceptibility is limited to persons between about ages 11 and 45. MS on the Faroe Islands has occurred as four successive epidemics beginning in 1943. The disease appears to have been introduced by British troops who occupied the islands for 5 years from 1940, and it has remained geographically localized within the Faroes for half a century. What was introduced must have been an infection, called the primary MS affection (PMSA), that was spread to and from successive cohorts of Faroese. In this concept, PMSA is a single widespread systemic infectious disease (perhaps asymptomatic) that only seldom leads to clinical neurologic MS. PMSA is also characterized by a need for prolonged exposure, limited age of susceptibility, and prolonged incubation. I believe that clinical MS is the rare late outcome of a specific, but unknown, infectious disease of adolescence and young adulthood and that this infection could well be caused by a thus-far-unidentified (retro)virus. Images

Epidemiologic evidence for multiple sclerosis as an infection.

Epidemiology of spinal cord injury

IN 1955 a disability status scale for multiple sclerosis was published that delineated 10 progressive steps or grades of overall neurologic dysfunction attributable to this disease.1 This was later elaborated233 to include a complementary system of grades within 8 “functional systems” of involvement: pyramidal, cerebellar, brainstem, sensory, bowel and bladder, visual, mental, and other. Since these scales have attained a modest popularityl-7 it seemed advisable to record certain changes suggested by further experience.

Further notes on disability evaluation in multiple sclerosis, with scale modifications.

A NECESSARY PREREQUISITE in establishing the efficacy of therapeutic measures in disease is accurate knowledge of the life history of the disease. This course is determined optimally by quantifying the amount of tissue destroyed or disrupted by the process at separate times in one or many patients. Such tissue change may be inferred in many ways. With an illness uniformly fatal in a limited time, survival rates are an appropriate measure of the disease. With other diseases, the clinical laboratory or radiologic evidence provides objective data. In multiple sclerosis, however, there are no auxiliary tools which will even establish the diagnosis, let alone measure severity at one point in time. Abnormalities of the cerebrospinal fluid, while often aiding in supporting the diagnosis by means of elevated gamma globulin or abnormal colloidal gold curve, are far from pathognomonic and, even when present, are not as yet at least correlated with the severity or duration of this disorder. Similarly, there is no method of predicting the future of an individual afflicted with this disease, although crude criteria of life expectancy, exacerbation rates, or incapacity have been offered as standards for groups. Even if these group predictions were valid (and most have been from retrospective studies), they would still be unsatisfactory for evaluating therapy, since many years’ observation is required by such approaches. However, a quantitative evaluation of severity of the disease process a t two or more points in time could provide, for large groups under simultaneous evaluation, a reliable indication of the results of therapy. Based principally on the material to be presented, it is estimated that some 200 patients followed for two years could suffice to give a definitive answer as to efficacy in a well-designed double-blind study.

John F. Kurtzke

Papers

Rating neurologic impairment in multiple sclerosis An expanded disability status scale (EDSS)

Epidemiologic evidence for multiple sclerosis as an infection.

Epidemiology of spinal cord injury

Further notes on disability evaluation in multiple sclerosis, with scale modifications.

On the evaluation of disability in multiple sclerosis