Search

La neuromielitis óptica (NMO) afecta a adultos jóvenes con una edad media de inicio mayor para esclerosis múltiple (EM), siendo entre 35 a 47 años. Afecta en relación 1.4:1 en mayor medida al género femenino. La incidencia y prevalencia de NMO no está bien establecida. Objetivos: describir las características clínicas y paraclínicas, impacto funcional de los cursos monofásico y recurrente de los pacientes con diagnóstico de NMO evaluados en el Instituto Nacional de Neurología y Neurocirugía en el periodo comprendido entre 1993 a 2005. Material y métodos: realizamos un estudio descriptivo, retrospectivo parcial en pacientes con diagnóstico de enfermedad de Devic en el Instituto Nacional de Neurología y Neurocirugía (INNN) evaluados entre enero 1993 y enero 2005. Resultados: el 71% de los pacientes correspondieron al género femenino y 29% al masculino. El evento clínico inicial más frecuente fue mielitis (44%). 23 pacientes tuvieron curso monofásico y 11 recurrente. La media de discapacidad en el curso monofásico fue de 5.8 y para el curso recurrente fue de 4.5 al inicio y 5.7 al final. Discusión: las principales diferencias con otros reportes son que el curso monofásico es más frecuente que el recurrente, mayor discapacidad en el grupo recurrente, la edad de presentación es 3 años mayor que lo reportado. Conclusiones: este es el primer reporte epidemiológico en México de pacientes con diagnóstico de enfermedad de Devic, encontramos algunas diferencias con los reportes previos fundamentalmente en la edad de presentación, curso clínico prevalente y evidencia de enfermedades autoinmunes concomi-tantes. [ABSTRACT FROM AUTHOR]

The Disability Status Scale for multiple sclerosis was the direct result of World War II, in which 16.4 million persons served in the US military. Thereafter academic medicine enabled the modernization of the Veterans Administration in patient care, research, and training. Under the GI Bill, I attended Cornell University Medical College, where there was an intensive course in neurological diagnosis requiring detailed recording of positive and negative findings. This was used in junior and senior clinical clerkships and residency training, all of which I took at the Bronx VA Hospital. During my residency we assessed a possible treatment for MS, which required a comparison group and a means of measuring change. The former comprised the records of over 300 MS patients, whose neurological deficits were then consolidated into mutually exclusive Functional Systems, each with grades for severity. As rank-order scales they could not be summed or compared directly, but they were used as the basis for the DSS, which ranged from 0 (normal) to 10 (death due to MS). This scale was later expanded into the EDSS by halving each step 1 through 9. This bifid system is applicable to all patients with MS regardless of type or severity of neurological impairment.

Geographically MS describes three frequency zones. High frequency areas (prevalence 30+ per 100 000) now comprise most of Europe, Israel, Canada, northern US, southeastern Australia, New Zealand, and easternmost Russia. Medium frequency areas include southern US, most of Australia, South Africa, the southern Mediterranean basin, Russia into Siberia, the Ukraine and parts of Latin America. Prevalence rates under 5 per 100 000 are found in the rest of Asia, Africa and northern South America. Migrants from high to lower risk areas retain the MS risk of their birth place only if they are at least age 15 at migration. Those from low to high increase their risk even beyond that of the natives, with susceptibility extending from about age 11 to 45. Thus MS is ordinarily acquired in early adolescence with a lengthy latency before symptom onset. MS occurred in epidemic form in North Atlantic islands: probably in Iceland and the Shetland-Orkneys; clearly in the Faroe Islands. In the Faroes first symptom onset was in 1943, heralding the first of four successive epidemics at 13 year intervals. The disease was presumably introduced by occupying British troops during World War II, with the postwar occurrences representing later transmissions to and from consecutive cohorts of Faroese. What was transmitted is thought to be a specific, widespread, persistent infection called PMSA (the primary multiple sclerosis affection) which only rarely leads years later to clinical MS. Search for PMSA is best attempted on the Faroes where there are regions still free of MS after 50 years.

In previous papers of this series, we explored the epidemiology of MS, examining the effects of race, sex, geography, latitude and climate, migration, age at onset, population ancestry, and individual ethnicity on the risk of MS, using an unusually large cohort of MS cases and pre-illness matched controls comprising US veterans of World War II (WWII) and the Korean Conflict (KC). In this paper, we examine primarily the effect of other factors on the risk of MS in this cohort and their relation to those previously studied. We found here that latitude tier of residence at entry into active duty (EAD), years of education, and socioeconomic class (coded from occupation) were similarly associated with MS risk among white men, black men, and white women. Higher levels of each factor showed increased MS risk. Multivariate analyses indicated that for white male WWII subjects an urban address, 9 or more years of education, uncorrected visual acuity less than 20/20 at EAD, a more northern latitude, and a higher proportion of the subject's EAD state population reporting Swedish ancestry each significantly increased the risk of MS. White male KC subjects showed roughly the same patterns, except that uncorrected visual acuity less than 20/20 was associated with lower MS risk (ancestry/ethnicity was not studied). For black male WWII and KC subjects combined, a similar analysis (omitting ancestry/ethnicity) showed that only latitude at EAD and 9 or more years of education were independently associated with a significantly higher MS risk, and for WWII plus KC white women (also without ancestry/ethnicity), only latitude was a significant risk factor in these multivariate analyses. The smaller number of subjects, especially in these last two groups, limited the power to detect statistically significant risks in these last analyses. Similarities to white men of WWII in univariate analyses for all other groups suggest that findings for the former would otherwise apply to the latter. Although the interpretations of these associations may be obscure, in addition to geography, age, sex, and race, per se, higher socioeconomic status is significantly associated with higher MS risk in black and white men and in white women in the United States.

Neuroepidemiology is the application of the methods of epidemiology to the problems of clinical neurology. After diagnosis, the most basic characterization of a disease is its frequency. This characterization requires ascertainment of case (numerator) within their population at risk (denominator) to provide incidence, prevalence, and mortality rates. Mortality rates come from government publications, and morbidity rates (incidence and prevalence) from specific field surveys. Definition of the course of illness and identification of risk factors for occurrence or course require specific studies and appropriate statistical testing.

Previously, we studied the effect of population ancestry on the risk of multiple sclerosis (MS) in US veterans of World War II, comparing by state 1980 US census ancestry data with MS case/control ratios. Here, the joint effects of population ancestry and surname-derived ethnicity on MS risk are examined in the same series. Census data are used again to characterize the population ancestry of the state from which each subject entered active duty (EAD)--that is, the proportions of the populace reporting various ancestries--and subjects were also individually categorized into a single ethnic group, without knowledge of case/control status, based on surname. In this study population, categorized ethnicity was strongly correlated with population ancestry, as expected. Although univariate analyses showed statistically significant associations between MS risk and several surname-derived ethnicities and ethnic groups, when residence at EAD was accounted for as well, there was almost no ethnic variation in MS risk. A logistic regression analysis further showed that variations in MS risk are associated most strongly with latitude and population ancestry group; in particular, subjects who entered military service from states with higher proportions of Swedish or French ancestry had higher risks of MS. After adjustment for characteristics of place, the only significant individual ethnicity factor found was Southern European ethnicity. In general, we conclude that an individual's ethnicity seems to be of less relative importance in determining MS risk than is the population ancestry of the state of EAD. These findings underscore the fact that MS is a disease of place, with 'place' including not only attributes of the locale (e.g., latitude), but also of its populace (e.g., ancestry).

Clinically, the Schumacher Panel criteria remain the best set of diagnostic criteria. Two subsets therein are definable, i.e., exacerbating-remitting (ER) and chronic progressive (CP), with the latter subdivided into progressive from onset and secondarily progressive. A clinically stable stage can also be recognized. It has been customary in treatment trials to separate ER and CP patients. End point for the latter is a comparison of neurologic status at the end of the trial with that entry. A similar assessment can be made for ER patients. With this criterion both types could be included in a single study. One could also, though, treat the exacerbation in an acute study or assess whether exacerbations can be prevented in a long-term trial. Most clinicians no longer consider monophasic disease as multiple sclerosis (MS). Depending on clinical extent, such patients are divisible into acute disseminated encephalomyelitis, Devic disease, transverse myelopathy, or optic neuritis. Each subgroup could be studied as with an acute exacerbation or in long term as to whether future and different neurologic insults can be prevented. One measure of neurologic status is the Disability Status Scale (DSS), which grades clinical impairment due to MS on a 0 (normal) to 10 (death due to MS) basis. The expanded DSS (EDSS) subdivides each step 1 through 9 into two. Type and severity of neurologic impairment is defined by graded involvement in the following eight functional systems (FS): pyramidal, cerebellar, brainstem, sensory, bowel and bladder, visual, cerebral, and other. Frequency and severity of each FS correlates strongly with DSS scores.(ABSTRACT TRUNCATED AT 250 WORDS)

Epidemiology is the study of the natural history of disease or injury. For a given disorder, this includes its definition, frequency, severity, course and risk factors. Only population-based rates provide data that can be compared among studies. These rates are the incidence or attack rate, the mortality or death rate, and the prevalence rate. For stroke even these rates are not comparable unless they are age-adjusted to a common base. Risk factors are attributes associated with the occurrence of the disease. Relative risk calculation requires population-based rates or a population cohort followed prospectively. For retrospective case-control comparisons the odds ratio is used as an approximation of relative risk. Mortality rates for stroke are widely available and can give a first estimate of risk by geographic location, age, sex and race. In death data, only the sum of all stroke deaths is sufficiently valid for use, while the components are more often wrong than right, except for subarachnoid hemorrhage. International death rates show considerable variation, the highest rates occurring in the Orient. Rates in many countries declined between the 1950s and 1970s but in others, like Portugal, they increased. Stroke deaths in the United States hae been declining rather steadily since the 1920s and continue to do so to the present.

Self-reported ancestry data for the U.S. population from the 1980 decennial census and multiple sclerosis (MS) risk data derived from a large series of World War II white male veterans with MS and matched controls were aggregated on a state level and analyzed to determine the relationship between ancestry and MS risk. A significant portion of the state-by-state variation in MS risk is explainable statistically by differences in ancestry among state populations, even when geographic latitude is included in analyses. In the main, Swedish and other Scandinavian ancestry is most consistently associated with places with increased MS risk. In some analyses, Italian, French, and (to a lesser extent) Scottish ancestries are also associated with increased risk, whereas English and Dutch ancestries are each associated with decreased risk, but most of these non-Scandinavian correlations may reflect predominantly geography per se. These findings provide evidence that ancestry of the resident population, a confounded measure of genetic susceptibility and cultural environment, is part of the complicated picture of MS as a disease of place.

Background: Nonrheumatic atrial fibrillation is common among the elderly and is associated with an increased risk of stroke. We investigated whether anticoagulation with warfarin would reduce this risk., Methods: We conducted a randomized, double-blind, placebo-controlled study to evaluate low-intensity anticoagulation with warfarin (prothrombin-time ratio, 1.2 to 1.5) in 571 men with chronic nonrheumatic atrial fibrillation; 525 patients had not previously had a cerebral infarction, whereas 46 patients had previously had such an event. The primary end point was cerebral infarction; secondary end points were cerebral hemorrhage and death., Results: Among the patients with no history of stroke, cerebral infarction occurred in 19 of the 265 patients in the placebo group during an average follow-up of 1.7 years (4.3 percent per year) and in 4 of the 260 patients in the warfarin group during an average follow-up of 1.8 years (0.9 percent per year). The reduction in risk with warfarin therapy was 0.79 (95 percent confidence interval, 0.52 to 0.90; P = 0.001). The annual event rate among the 228 patients over 70 years of age was 4.8 percent in the placebo group and 0.9 percent in the warfarin group (risk reduction, 0.79; P = 0.02). The only cerebral hemorrhage occurred in a 73-year-old patient in the warfarin group. Other major hemorrhages, all gastrointestinal, occurred in 10 patients: 4 in the placebo group, for a rate of 0.9 percent per year, and 6 in the warfarin group, for a rate of 1.3 percent per year. There were 37 deaths that were not preceded by a cerebral end point--22 in the placebo group and 15 in the warfarin group (risk reduction, 0.31; P = 0.19). Cerebral infarction was more common among patients with a history of cerebral infarction (9.3 percent per year in the placebo group and 6.1 percent per year in the warfarin group) than among those without such a history., Conclusions: Low-intensity anticoagulation with warfarin prevented cerebral infarction in patients with nonrheumatic atrial fibrillation without producing an excess risk of major hemorrhage. This benefit extended to patients over 70 years of age.

Age at onset of multiple sclerosis (MS) symptoms was ascertained for subsets of some 4,400 veterans of World War II who had been adjudged 'service-connected' for this condition. Average age at onset was 27.0 years for white men, 27.7 for white women, and 27.5 for black men. The unexpectedly older age for women is attributed to their older age at entry into service. When the coterminous United States was divided into three horizontal tiers of states, we found a strong effect of geography on age at onset. By state of residence at entry into active duty (EAD), white men had an average age at onset of 26.4 years in the northern tier, 27.3 years in the middle, and 28.8 years in the south. Trends were similar for white women and black men. Migrants, defined as those whose birth and EAD tiers differed, showed increasing ages at onset with southward moves. A statistical model used to discriminate between the influence of birth and EAD tiers on age at onset confirmed the significant effect of EAD alone. These data are compatible with the theses that the cause of MS is less common (or less efficient) in locations where the clinical disease is less common, and that its acquisition therefore occurs at an older age in those locales.

Using data from 32 patients with symptom onset between 1943 and 1973, we described the occurrence of clinical neurologic multiple sclerosis (CNMS) in the Faroe Islands as then constituting three epidemics. We concluded that CNMS is the rare late result of infection with the primary MS affection (PMSA), a state requiring some 2 years of exposure for acquisition by Faroese. Our theses are that PMSA was first transmitted during World War II by affected by asymptomatic British troops to Faroese aged 11-45; that this (F1) cohort of affected asymptomatic Faroese under age 27 in 1945 transmitted PMSA to the next (F2) cohort of Faroese comprising those attaining age 11 each year from 1945 until F1 input ceased; that the F2 cohort similarly transmitted PMSA to the third (F3) cohort of Faroese. Cases of CNMS defining epidemics I-III were members of the respective F1-F3 cohorts. Within the F4 cohort of Faroese there is now a fourth epidemic of CNMS, with 7 patients with symptom onset between 1984 and 1989. Intermittency of the year of birth for CNMS cases is thus a reflection of membership in these separate population cohorts, and does not indicate 'protection' in infancy or childhood. There is no evidence for an extra-Faroese source of MS after the first epidemic. No model of acute infection with short transmissibility fits the data.

Based primarily on a survey of all neurology residency training programs in the United States conducted in 1985-1986, the average annual production (incidence) of general neurologists for 1980-1986 was 363.6 and of child neurologists for 1982-1986, 53.8. About 1/4 of these general neurologists and 1/3 of child neurologists are women; about 1/4 of either are foreign medical graduates, predominantly foreign-born. Data routinely published by the AMA well match the questionnaire information. First postgraduate year of training was in internal medicine for 2/3 of general neurologists. Board certification have recently averaged 290.9 (general) and 37.1 (child) per annum. From life-table calculations, prevalence of general neurologists in 1990 is estimated at 7,500 fully-trained and 5,500 board-certified, and of child neurologists near 1,100 trained and over 600 certified. The number of neurologists is predicted to plateau near the year 2020 at some 13,700 trained, including 1,700 child neurologists, and 9,800 certified (1,100 child). The maximal prevalence rate for all neurologists will be 4.75 per 100,000 population in 2010, declining then to 4.42 by 2050; those rates provide shortfalls of 30% and 35%, respectively, compared with previously calculated needs for neurologists.

Thin-section computed tomographic (CT) scans of 1.5 mm thickness were obtained in the study of 44 consecutive patients with Huntington's disease (HD) and six patients with sporadic progressive chorea and dementia. Mild to moderate midbrain and pontine atrophy, a dilated third ventricle, and enlarged quadrigeminal plate cisterns were observed in most cases suggesting that brainstem atrophy is common in HD. Brainstem atrophy preceding caudate atrophy in two cases and pontine or midbrain atrophy to a similar degree as caudate atrophy in eight cases suggest that brainstem atrophy may occasionally precede or appear at the same time as caudate atrophy. The CT scan brainstem findings and their neuropathologic confirmation suggests a more important role for the brainstem in the pathophysiology of HD.

Both mortality and morbidity data indicate quite clearly that multiple sclerosis is a geographically-related disease, and thus MS can be thought of as an acquired environmental (exogenous) illness. High frequency parts of the world for MS are Europe between 65 degrees and 45 degrees north latitude, northern United States and southern Canada, New Zealand, and southern Australia. These regions are bounded by medium frequency MS regions: in Europe to the north, east, and south; in America for southern U.S.; and the remainder of Australia. Latin America, Asia and Africa are essentially of low frequency from present data. Latitude is not a sufficient criterion: at 40 degrees north latitude, MS is high in America, medium in Europe, and low in Asia. All high and medium risk areas therefore are in Europe or European colonies; thus MS is the white man's burden spread from western Europe. Within the U.S., MS is less common among Negroes, Japanese, and possibly Amerindians than in whites regardless of geography. Migration studies among risk areas indicate that migrants keep much of the risk of their birthplace, but also that overall the risk is decreased by high-to-low migration, and probably increased by low-to-high. For the former, it seems that adolescence is the age critical for retention of birthplace risk. Some preliminary data on a possible epidemic of MS are also presented. All the epidemiologic information would be most easily explained if MS were an infectious (viral) illness with prolonged latency. The proof of this though must come from the laboratory.

Thin-section computed tomographic (CT) scans of 3 and 1.5 mm thickness were obtained using the Philips Tomoscan 310 and General Electric 8800 CT/T scanners in the study of 10 consecutive patients with progressive supranuclear palsy (PSP) and 31 patients with other diseases. Marked midbrain and moderate pontine atrophy, a dilated third ventricle, and enlarged quadrigeminal plate cisterns were observed in all PSP cases. The aqueduct was dilated in several. In six of the PSP cases, there was a striking midbrain abnormality in the form of a low-density area extending from the interpeduncular cistern toward the aqueduct. Thin-section metrizamide-enhanced cisternography of three of the six PSP cases showed that the low-density abnormality was the result of the interpeduncular cistern invaginating the atrophic midbrain.

Concerns have been raised as to our diagnoses, exclusions, case ascertainment, definition of epidemics, and the role of the British occupation in the occurrence of multiple sclerosis among Faroese. We believe none of these points are substantiated, but rather that there did occur three consecutive and decreasing epidemics of clinical neurologic MS (CNMS) among native resident Faroese between 1943 and 1973, with no cases before or (so far) since. We have attributed these occurrences to the introduction into the Faroe islands of what we have called the primary MS affection (PMSA) by the British troops who occupied the islands in World War II. The first Faroese population cohort of PMSA-affected, which included the epidemic I cases, transmitted PMSA to the next cohort of Faroese comprising those attaining age 11 in 1945-1956, and they included the epidemic II cases. The second cohort thereafter similarly transmitted PMSA to the third Faroese cohort with its epidemic III cases. We conclude that PMSA is a single, widespread, specific, systemic infectious disease whose acquisition in virgin populations follows 2 years of exposure starting between age 11 and 45, which then produces CNMS in only a small proportion of the affected after a 6-year incubation period, and which is transmissible only during part or all of this systemic PMSA phase that ends before the usual age of CNMS onset. In endemic MS areas both the exposure and incubation periods may be twice as long, but otherwise PMSA may have there the same characteristics as inferred for the Faroes.

Aphasic patients who met stringent selection criteria were assigned randomly to three groups: clinic treatment by a speech pathologist for 12 weeks, followed by 12 weeks of no treatment; home treatment by a trained volunteer for 12 weeks, followed by 12 weeks of no treatment; or deferred treatment for 12 weeks, followed by 12 weeks of treatment by a speech pathologist. At 12 weeks after entry, language measures indicated that the clinic-treatment patients made significantly more improvement than did the deferred-treatment patients, and improvement in home-treatment patients did not differ significantly from either clinic- or deferred-treatment patients. At 24 weeks after entry, after deferred-treatment patients had received clinic treatment, there were no significant differences among the groups. These results suggest that clinic treatment for aphasia is efficacious, and delaying treatment for 12 weeks does not compromise ultimate improvement.

The International Federation of Multiple Sclerosis Societies has been attempting to define a Minimal Data Set for multiple sclerosis following the tripartite scheme of the World Health Organization, with one rating scheme for neurologic signs, one for physical disabilities, and one for the societal impact of the disease. Current recommendations are the Disability Status Scale or the Expanded DSS plus Functional Systems for the first, Incapacity Status Scale of 16 items for the second, and Environmental Status Scale of 7 items for the third. All are graded in an ordinal (rank) scale from 0 (normal) with larger numbers for greater involvement. ISS scores range from 0-4 and ESS from 0-5 for each item. The only part of this scheme useful for measurement in clinical trials is the (E)DSS + FS. The DSS ranges from 0-10; EDSS subdivides each DSS grade 1-9 into two. FS are pyramidal, cerebellar, brain stem, sensory, bowel and bladder, visual, cerebral, or other; all save the last are graded 0-5 or 0-6. The DSS correlates well with both frequency and severity of involvement in all FS, which in turn represent a coded standard neurologic examination.

When reviewed some 10 years ago, available prevalence studies of multiple sclerosis (MS) seemed to divide the world into three frequency zones for MS: high prevalence at 30 to 60 per 100,000 population; medium at 5 to 15; and low at less than 5 per 100,000. In the last decade the number of the available studies has more than tripled. Their reassessment, including judgments of comparability, still indicates a high-medium-low division of MS frequency world-wide. The risk areas comprise northern Europe, northern United States, much of southern Canada, New Zealand, and probably southern Australia. Prevalence rates in these regions are mostly 30 to 80 per 100,000 population, centering at about 50. Medium frequency is defined as prevalence of 5 to 25, and is mostly 10 to 15. In Europe, the medium frequency zone bounds that of high frequency to the north, east, and south. The European Mediterranean basin is of medium prevalence with a sharp division from the high zone across France and Switzerland. It is likely that this division continues eastward across Austria, north of Hungary, and across the upper Ukraine to the Caspien Sea, but this is not definite. Medium risk areas of Europe thus include surveyed sites of Spain, Italy, Hungary, Jugoslavia, Bulgaria, and central Ukraine, together with southeastern France and southern Switzerland. Though Romania could be high, it is more likely to be of medium prevalence. Turkey measures low, but from incomplete data. From nationwide prevalence and mortality studies, the west coast of Norway and all Scandinavia above latitude 65 degrees north are of medium frequency. Based on hospital data, northwestern USSR is high, and central and southern USSR medium, in MS risk. Other medium risk areas include southern United States, most of Australia, one ethnic group only in South Africs, and possibly Hawaii. Low risk areas are allsurveyed sites of Asia, the Pacific islands, Africa, Latin America, Alaska, and Greenland.

The clinical manifestations of 24 cases and the autopsy findings of 6 cases of extremity myorhythmia are presented. Extremity myorhythmia is that form of myorhythmia in which rhythmic alternating movements predominantly involve the limbs. The main difference between the tremor of extremity myorhythmia and the tremor of parkinsonism is the slower tremor rate, 2 to 3 cycles/s in myorhythmia and 4 to 6 cycles/s in parkinsonism. The mechanograms, except for the slower frequencies in myorhythmia, can be very similar, including sinusoidal oscillation patterns in both conditions. Myorhythmia may be defined as a coarse, alternating tremor, present at rest and usually during movement, which occurs at rates varying from 50 to 240 oscillations/min but mostly at either 120 to 140 or 160 to 180 cycles/min. The alternating movements may be intermittent or continuous or both types may be present in different body parts. When multiple parts are involved, synchronous or asynchronous movements are about equally common. Movements are usually relatively rhythmic and regular but may vary over periods of time in rate, rhythm or amplitude and rarely so, even over the course of a few hours and are absent during sleep. Movements may involve single limbs, several limbs or a combination of limbs plus face, palate, head, jaw, neck, tongue, eyes or trunk. The frequency of the movements in the 24 cases varied from 120 to 180 oscillations/min with two exceptions the slowest being 60 and the fastest 240, with most tending to cluster near either 120 or 180 cycles/min. The most common aetiologies were brainstem vascular disease and cerebellar degeneration secondary to chronic alcoholism-nutritional deficiency. The best prognosis occurred in the latter group. Clinicopathological correlations in our autopsy series indicate that myorhythmia of the limbs may occur ipsilateral to the dentate nucleus or superior cerebellar peduncle lesions or contralateral to inferior olive involvement. Unilateral lesions of the dentate nucleus may result in bilateral limb movements and bilateral dentate lesions may be associated with unilateral limb movements. The frequent involvement of the cerebellum and the substantia nigra suggests possible roles for the cerebellum and substantia nigra in the myorhythmia process.

A 37-year-old man with a history of seizures developed periodic alternating nystagmus (PAN) along with other signs of primidone/phenobarbital toxicity. The PAN gradually diminished in cycle length and intensity, finally resolving with gradual discontinuation of the drugs.

There has been a hypothesis that Hodgkin's disease in young adults and multiple sclerosis may have related causes because the age of clinical onset and the geographic distribution of both are similar. This hypothesis was tested for data in Denmark. Detweeen 1943-62, the average annual incidence rate for Hoadgkin's disease in Denmark was 2.25 per 100,000 population (2.68 male and 1.83 female). Between 1951-69, the average annual death rate for Hodgkin's disease was 2.15 per 100,000 (2.66 male and 1.64 female). The average annual incidence rate for multiple sclerosis in Denmark was calculated from age at onset for 2,481 prevalent cases of 1949, the 1940 population, and an average annual incidence of 128.86 cases for 1939-45: the average annual incidence rate per 100,000 was then 3.35 (3.00 male and 3.69 female). Age specific incidence and death rate for Hodgkin's disease in Denmark each showed a bimodal curve, with one peak at age 25-29 and the other at age 70-74; this was found for each sex, with male rates consistently higher than female. The age specific incidence rates for multiple sclerosis were clearly unimodal with a peak at age 25-29 more definite in females than males. Rates for MS were notably higher for young females than males but about equal by sex for those over the age of 30. The geographic distribution of multiple sclerosis within the counties (amter) of Denmark was markedly non-random, with the major concentration of high prevalence areas middle Jutland and on to Fyn. Geographic distribution of Hodgkin's disease, whether for the young or the old, and whether from incident or death cases, showed no significant variation from a homogeneous distribution. In formal testing there was no correlation of any Hodgkin's distribution with that of MS. A review of the Hodgkin's data for distribution in the United States, on which the original hypothesis was based, suggests the variation there may be little more than reporting artifact. Accordingly, we conclude that there is no relation between distributions of these two disorders, and the factors they do appear to have in common are either quite non-specific or of questionable validity. Thus there is no reason to believe that multiple sclerosis and Hodgkin's disease, even in the young, share a common etiology.

Neurologists in the United States were enumerated for each year from 1935 to 1984 on two bases: board certification (including Child Neurology and Psychiatry and Neurology) and completion of PG4 neurology residency training. The annual incidence of new neurologists was calculated at less than 200 until 1970; then it rose steadily to 380 in 1980, and plateaued thereafter at 385. The estimated number of neurologists present at one time (prevalence) was 1,500 in 1950, 2,400 in 1970, 4,600 in 1980, 8,100 in 1990, and 11,000 in 2000. These numbers for total neurologists will plateau at 12,200 by about 2010, at which time the number of certified neurologists will also plateau at 9,900. Both numbers are notably less than our prior estimate of needs: 16,500 neurologists by 1990, 19,100 in 2010.

Palatal myoclonus associated with extremity movements such as myoclonus or tremor is uncommon and reports are rare. Five patients with palatal myoclonus and a rest tremor are presented. In four patients, a slow rest tremor (3 Hz or less) was present. The tremor persisted on sustained posture and finger-to-nose maneuvers and was usually not synchronous with the palatal movements. It was not associated with clinical manifestations of Parkinson's disease and occurred in conjunction with brain-stem infarction in three patients.