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Mycoplasmal infections may be complicated by a wide variety of systemic syndromes, including neurological disorders. Circumstantial evidence suggests that these are immunologically-induced. A detailed study of five patients with proven mycoplasma pneumoniae and central nervous system signs showed that immunological factors were involved and suggested that the neurological symptoms were due to a vasculopathy.

Objectives A history of prior fracture is one of the strongest predictors of a future fragility fracture. In FREEDOM, denosumab significantly reduced the risk of new vertebral, non-vertebral, and hip fractures. We carried out a post-hoc analysis of FREEDOM to characterize the efficacy of denosumab in preventing secondary fragility fractures in subjects with a prior fracture.Methods A total of 7808 women aged 60–90 years with a bone mineral density T-score of less than − 2.5 but not less than − 4.0 at either the lumbar spine or total hip were randomized to subcutaneous denosumab 60 mg or placebo every 6 months for 36 months. The anti-fracture efficacy of denosumab was analyzed by prior fracture status, to assess secondary fragility fracture, and by subject age, prior fracture site and history of prior osteoporosis medication use.Results A prior fragility fracture was reported for 45% of the overall study population. Compared with placebo, denosumab significantly reduced the risk of a secondary fragility fracture by 39% (incidence, 17.3% vs. 10.5%; p < 0.0001). Similar results were observed regardless of age or prior fracture site. In the overall population, denosumab significantly reduced the risk of a fragility fracture by 40% (13.3% vs. 8.0%; p < 0.0001), with similar results observed regardless of history of prior osteoporotic medication use.Conclusions Denosumab reduced the risk of fragility fractures to a similar degree in all risk subgroups examined, including those with prior fragility fractures. Identifying and treating high-risk individuals could help to close the current care gap in secondary fracture prevention.

Human immunoglobulin G (IgG) Fc receptor IIa (Fc gamma RIIa; CD32) is expressed on phagocytes, triggers phagocytosis, and represents the sole Fc receptor for IgG (Fc gamma R) capable of interaction with IgG2, the main IgG subclass induced in response to bacterial capsular polysaccharides. The two genetically determined structurally different allotypes of human Fc gamma RIIa, the products of the Fc gamma RIIa-R131 and IIa-H131 alleles, have functionally different reactivities with human IgG2. In humans, the Fc gamma RIIa-H131 allotype is known to interact efficiently with complexed human IgG2, whereas the IIa-H131 allotype does so only poorly. This polymorphism may therefore have implications for IgG2-mediated phagocytosis of encapsulated bacteria and susceptibility to bacterial infections. Phagocytosis of IgG2-opsonized bacteria by homozygous Fc gamma RIIa-R/R131, heterozygous IIa-H/R131, and homozygous IIa-H/H131 polymorphonuclear cells (PMN) was compared. A higher phagocytic capacity of IgG2-opsonized group B type III streptococci by PMN of homozygous H/H131 individuals compared with PMN from homozygous R/R131 individuals was observed (P = 0.001), while heterozygous IIa-H/R131 PMN showed intermediate phagocytosis. In this model system, IgG2-mediated phagocytosis was independent of the Fc gamma RIIIb-NA1/NA2 allelic polymorphism.

Anti-group B streptococcal type III polysaccharide-specific human B cells from the peripheral circulation can be activated and detected in an in vitro culture system. It is possible to detect both IgM- and IgG- producing cells from both seropositive and seronegative donors. The specificity of the response was demonstrated by inhibition with excess liquid phase antigen and the use of related but antigenically distinct control antigens. The response was absent without the addition of T cells, optimal at 10% and 25% T cells respectively for IgM- and IgG-secreting cells, and undetectable using 50% T cells. The optimal antigen concentration for in vitro B-cell activation is 2.5 x 10(-4) micrograms/ml. Cells from 5 of 6 seropositive donors and 3 of 7 seronegative donors produced specific IgM antibody after culture with antigen. We conclude that the control of the human antibody response to the group B streptococcal type III polysaccharide is influenced by T cells. The response seen in the culture system may be of value in assessing future vaccine candidates designed to prevent neonatal infections.

To the Editor: We read with interest the article by Miller et al. describing the effect of l-dopa on plasma homocysteine in Parkinson disease (PD).1 We welcome the attention that this important metabolic phenomenon now receives, as we think that l-dopa–induced hyperhomocystenemia in PD is indicative of a broader metabolic alteration of the trans- methyl pathway with potential clinical consequences that extend beyond vascular disease and dementia. As reported by the authors,1 the increase in homocysteine is due to l-dopa O - methylation, a reaction catalyzed by catechol- O -methyltransferase (COMT). This reaction consumes the methyl donor S-adenosylmethionine, the principal methyl-group donor in the brain, and leads to increased production of (demethylated) S- adenosylhomocysteine, and, ultimately, homocysteine. Increased O -methylation, however, cannot only lead to hyperhomocystenemia, but can also cause a depletion of S- adenosylmethionine, inducing a state of relative hypomethylation. In addition to COMT- dependent O -methylation of catecholamines, S-adenosylmethionine is the methylating agent in vital metabolic reactions, including the synthesis of phosphatidylcholine and creatine, the methylation of phospholipids and of proteins, including N- and carboxyl- methylation of proteins, essential for the proper function of receptors configuration and permeability of ion channels.2 Of immediate clinical relevance is the fact that S- adenosylmethionine depletion has been associated with depression, common in patients with Parkinson …

Objective: To examine patterns of familial aggregation and factors influencing onset age in a sample of siblings with PD. Methods: Sibling pairs (n = 203) with PD were collected as part of the Gene PD study. Standardized family history, medical history, and risk factor data were collected and analyzed. Results: The mean age at onset was 61.4 years and did not differ according to sex, exposure to coffee, alcohol, or pesticides. Head trauma was associated with younger onset ( p = 0.03) and multivitamin use with later onset ( p = 0.007). Age at onset correlation between sibling pairs was significant ( r = 0.56, p = 0.001) and was larger than the correlation in year of onset ( r = 0.29). The mean difference in onset age between siblings was 8.7 years (range, 0 to 30 years). Female sex was associated with increased frequency of relatives with PD. The frequency of affected parents (7.0%) and siblings (5.1%) was increased when compared with frequency in spouses (2.0%). Conclusions: The greater similarity for age at onset than for year of onset in sibling pairs with PD, together with increased risk for biological relatives over spouses of cases, supports a genetic component for PD. Risk to siblings in this series is increased over that seen in random series of PD cases; however, patients in this sample have similar ages at onset and sex distribution as seen for PD generally. These analyses suggest that factors influencing penetrance are critical to the understanding of this disease.

Coagulase negative staphylococci are the commonest blood culture isolate from infants on neonatal intensive care units. The differentiation of contaminants from isolates representing true infection remains a significant clinical problem. Data from two neonatal intensive care units were collected prospectively in order to find those parameters, which best correlated with actual sepsis. Each case was assessed using clinical parameters to categorise infants into infection and contaminant groups. Logistic regression was then performed to find significant correlates. Three correlates were found, namely the presence of a long line (P = 0.001), abnormal white cell count (P = 0.037) and abnormal white cell morphology (P = 0.027). Abnormal white cell morphology was assessed by two experienced hematologists. More than half the isolates were probable contaminants and true infection may occur in the absence of a long line in this patient group.

Controversy persists about the etiology of Parkinson's disease (PD). Pesticides, herbicides, well-water consumption, head injury, and a family history of PD have been reported as risk factors for PD. The purpose of this study was to (1) investigate the impact of environmental factors on PD risk (2) estimate the chronology, frequency, and duration of those exposures associated with PD; and (3) investigate the effects of family history on PD risk. One-hundred and forty PD cases were recruited from Boston University Medical Center. The control group was composed of 147 friends and in-laws of PD patients. Environmental, medical, and family history data were obtained by structured interview from each participant for events recalled prior to PD onset for cases, or corresponding censoring age for controls (mean age = 56 years of age for each group). A traditional stratified analysis, adjusting for birth cohort and sex, was employed. Four factors were associated with increased risk for PD: (1) head injury (OR=6.23, confidence interval [CI]: 2.58-15.07); (2) family history of PD (OR=6.08, CI: 2.35-15. 58); (3) family history of tremor (OR=3.97, CI: 1.17-13.50); and (4) history of depression (OR=3.01, CI: 1.32-6.88). A mean latency of 36. 5 (SE=2.81) years passed between the age of first reported head injury and PD onset. A mean latency of 22 (SE=2.66) years passed between the onset of the first reported symptoms of depression and onset of PD. Years of education, smoking, and well-water intake were inversely associated with PD risk. PD was not associated with exposure to pesticides or herbicides. These findings support the role of both environmental and genetic factors in the etiology in PD. The results are consistent with a multifactorial model. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 88:742-749, 1999.

The reduction or loss of cytochrome P450 enzyme activity as a result of mutations in the CYP2D6 gene has been suggested as a risk factor for Parkinson's disease (PD). Conflicting results among reported studies of the prevalence of mutations among patients with PD suggested a more comprehensive genotyping and an analysis of the interactions with other suspected risk factors and family history. We determined the frequency of seven CYP2D6 mutations among 109 patients with PD and 110 control subjects. Family history of PD, age of onset, exposure to pesticides or herbicides, and well-water consumption were obtained for all cases. There was no significant difference in frequency between patients with PD and control subjects for any mutant allele and no significant association with family history, onset age, or environmental exposures. We sought to increase the power of our study by combining reports from the literature, choosing allele frequencies as the most informative measure. Although we found variability in reported allele frequencies for control subjects that made a meta-analysis problematic, summing all reports demonstrated no difference in CYP2D6 mutation frequency between patients with PD and control subjects. This comprehensive study of CYP2D6 mutations demonstrates that other genes or shared environmental exposures account for the familial risk of PD.

Electrophysiologic confirmation of arsenic neuropathy has been well documented (LeQuesne and McLeod, 1977; Murphy et al.,1981; Donofrio et al.,1987; Gherardi et al.,1990; Oh, 1991; Lagerkvist and Zetterlund, 1994). Peripheral neuropathy associated with arsenic exposure primarily involves axons, with secondary change in the myelin sheath. Nerve impulses are conducted, therefore, only by the remaining undamaged fibers and not by those that are damaged. The resultant recording will show a reduction in the amplitude (in µV) of the evoked nerve action potential or even an absence of an evoked nerve action potential, depending upon the intensity of exposure and the severity of neuropathy. The conduction velocity of an individual nerve fiber may be reduced or completely blocked. However, the slowing may be relative and still be considered within normal range, depending upon how many axons are affected. Subtle differences can be overlooked unless a critical approach is taken. Upon statistical analysis, groups of affected persons may reveal significant differences from referent groups of unexposed persons, although the values for individuals within the group may be considered in a normal range. In such instances it is often necessary to use statistical analyses to identify differences and to ascertain any significance in these differences in arsenic-exposed populations (Feldman et al., 1979; Lagerkvist and Zetterlund, 1994).

Relationships between in vitro parameters (opsonic activity and anti-pneumococcal polysaccharide [PS] antibody subclasses) and in vivo mouse protection were established by logistic regression analysis. Data were from 158 mice challenged with pneumococci after vaccination with synthetic oligosaccharide- and PS-protein conjugates in combination with the adjuvant Quil A. The hypothesis that serum opsonic activity has predictive value for protection against pneumococcal infection was tested. Serum opsonic activity was well correlated with protection (chi 2 = 35.5, P < 0.001), although a stronger correlation was observed for anti-PS IgM and IgG. The combined use of IgG and opsonic activity as predictor variables yielded the best fitting model for predicting protection (chi 2 = 74.1, P < 0.001). When opsonic activity data were added to models that included various antibody isotypes, the statistical significance of the models was enhanced. Thus, the opsonic activity of antisera induced by pneumococcal vaccines can predict mouse protection.

Streptococcus pneumoniae type 23F capsular polysaccharide (PS23F) consitss of a repeating glycerol-phosphorylated branched tetrasaccharide. The immunogenicities of the following related antigens were investigated: (i) a synthetic trisaccharide comprising the backbone of one repeating unit, (ii) a synthetic tetrasaccharide comprising the complete repeating unit, and (iii) native PS23F (all three conjugated to keyhole limpet hemocyanin [KLH]) and (iv) formalin-killed S. pneumoniae 23F. All antigens except the trisaccharide-KLH conjugate induced relatively high anti-PS23F antibody levels in rabbits. The epitope specificity of such antibodies was then studied by means of an inhibition immunoassay. The alpha(1-->2)-linked L-rhamnose branch was shown to be immunodominant for immunoglobulin G (IgG) induced by tetrasaccharide-KLH, PS23F-KLH, and killed S. pneumoniae 23F: in most sera L-rhamnose totally inhibited the binding of IgG to PS23F. Thus, there appears to be no major difference in epitope specificity between IgG induced by tetrasaccharide-KLH and that induced by antigens containing the polymeric form of PS23F. Human anti-PS23F IgG (either vaccine induced or naturally acquired) had a different epitope specificity: none of the inhibitors used, including L-rhamnose and tetrasaccharide-KLH, exhibited substantial inhibition. These observations suggest that the epitope recognized by human IgG on PS23F is larger than the epitope recognized by rabbit IgG. Both human and rabbit antisera efficiently opsonized type 23F pneumococci, as measured in a phagocytosis assay using human polymorphonuclear leukocytes.

A chemistry student was acutely exposed to vapors of an organotin compound. Seventy-two hours later, he exhibited delirium, spatial disorientation, perseveration, inappropriate affect, and memory defects. Five months later, he experienced episodes of complex partial seizures, which continue to require anticonvulsant medication after 7 years. Trimethyltin was identified in blood and urine samples taken 17 days after the accident; the blood level of trimethyltin was elevated 35 days after exposure. Serial electroencephalograms showed persistent left temporal paroxysmal epileptogenic potentials. Serial neuropsychological tests revealed persistent memory defects, cognitive dysfunction, and dysphoria 4 years after exposure. We review acute, resolving, and long-term residual neurotoxic effects of trimethyltin in man. We describe detailed clinical observations, serial neuropsychological test results, electroencephalographic findings, and exposure data in this patient, confirming the limbic system effects of trimethyltin and relating them to the known histopathologic pattern of this condition.

(1973). Reduction of Muscle Artifact in Electroencephalographic Recording. American Journal of EEG Technology: Vol. 13, No. 1, pp. 13-26.

Following a 1978 outbreak of bladder neuropathy among workers exposed to dimethyl-aminopropionitrile (DMAPN), follow-up studies were performed 2 a after the original epidemic to evaluate the persistence of symptoms among a small group of initially affected workers. Although the overall prevalence of urologic and neurological symptoms fell for the 11 persons interviewed, significantly high rates of persistent symptoms were seen. Of particular concern was the increase in the prevalence of symptoms of sexual dysfunction. Physical examination identified one individual with sensorimotor neuropathy which was initially detected 2 a earlier. Three individuals who had similar neuropathic findings in 1978 were normal 2 a later. Objective neurophysiological and urologic testing revealed evidence of persistent abnormalities in several workers, but most of the objective findings had improved over the 2-a period. The follow-up of residual effects of occupational exposure to neurotoxic substances is essential to the understanding of the course of occupational illnesses.

Cerebral glucose metabolic rate (CMRGlu), measured by positron emission tomography, was bilaterally and symmetrically reduced in two patients with autosomal dominant Alzheimer's disease. Supramarginal gyri and temporal lobes were most severely affected. An isolated reduction of CMRGlu in the left supramarginal gyrus was observed in one asymptomatic at-risk subject.

To facilitate the early detection of neurotoxicity in workers exposed to hazardous substances, we assembled a set of noninvasive neurobehavioral tests designed to assess memory, verbal concept formation, visuomotor performance, and mood. The tests were administered to an unexposed reference population and multivariate prediction equations were developed to control for effects of age, gender, and education. To define the briefest test set with appropriate sensitivity and specificity, we applied factor analysis and stepwise logistic regression to data from our referents and a group of lead-exposed workers. As a result, we have identified a comprehensive set of tests that can be administered in less than 40 minutes by trained medical technicians on plant premises and used to detect the early effects of neurotoxic substances on exposed workers. Guidelines for applying this technique to common work-place exposures, including other metals and organic solvents, are discussed.

To evaluate the effects of chronic lead exposure on the nervous system in adults, a set of neurobehavioural and electrophysiological tests was administered to 99 lead exposed foundry employees and 61 unexposed workers. Current and past blood lead concentrations were used to estimate the degree of lead absorption; all previous blood lead concentrations had been less than or equal to 90 micrograms/100 ml. Characteristic signs (such as wrist extensor weakness) or symptoms (such as colic) of lead poisoning were not seen. Sensory conduction in the sural nerve was not affected. By contrast, various neurobehavioural functions deteriorated with increasing lead burden. Workers with blood lead concentrations between 40 and 60 micrograms/100 ml showed impaired performance on tests of verbal concept formation, visual/motor performance, memory, and mood. Thus impairment in central nervous system function in lead exposed adults occurred in the absence of peripheral nervous system derangement and increased in severity with increasing lead dose.

Two hundred and fifty six unselected women, 50 of whom had urinary symptoms (frequency of urination or dysuria, or both), and who were attending a department of genitourinary medicine, were investigated. The urinary symptoms were associated both with pyuria and the isolation of undoubted pathogens from midstream urine (MSU) specimens. No associations were found between urinary symptoms and the isolation of Neisseria gonorrhoeae or Chlamydia trachomatis from the urethra or cervix; the recovery of Mycoplasma hominis from the urethra, cervix, or MSU; the recovery of Trichomonas vaginalis or Candida albicans from the vagina; or the presence of bacterial vaginosis. Urethral leucocytosis was associated with the isolation of T vaginalis but not with the recovery of N gonorrhoeae, C trachomatis, C albicans, or urinary pathogens. Pyuria was associated with the isolation of urinary pathogens and with the presence of trichomoniasis; it was not associated with the recovery of C trachomatis or M hominis.

There are several categories of neurologic dysfunction which have been associated with metal intoxication. Many examples of case histories or animal studies where toxicity by metals has produced clinical manifestations and pathophysiologic changes similar to those found in certain primary neurological disorders have been reported. It is easy to make a diagnosis of metal intoxication in a subject whose work history and circumstances of exposure to specific substances is known. Observation of defined safety standards and time weighted averages for a work day in conjunction with environmental monitoring procedures are intended to reduce risk of undue absorption of known potential intoxicants. However, when a patient is seen by a physician and a probable neurological diagnosis is to be made in the absence of a detailed life-work history, the possible relationship to previous or current intoxication may be overlooked. This communication will review several neurological syndromes which have been found in association with metal accumulation.

Three cases of a syndrome resembling neuroleptic malignant syndrome are described in patients never exposed to neuroleptics. Each patient had a long history of Parkinson's disease treated with a carbidopa-levodopa combination. Two patients developed the syndrome when administration of the drug was discontinued temporarily. One developed the syndrome before the "drug holiday," and then died during the holiday because of this complication.

A large number of benzodiazepines have undergone clinical trials for a wide variety of neurological disorders. This chapter is confined to the three principal uses of benzodiazepines for neurological disorders in the United States. These are: (1) clonazepam as a chronic oral antiepileptic drug, (2) intravenous diazepam for status epilepticus, and (3) diazepam for spasticity.

Forty-three patients affected with Alzheimer's disease were identified in a kindred of Italian origin, emigrated in part to the U.S.A. and France. Thirteen were known by history, 21 by medical record, and 9 by personal examination, of whom 5 were confirmed histopathologically. The clinical picture was fairly uniform: the first symptom was memory loss beginning around age 40. Psychotic-like symptoms often followed, with rapid evolution into profound dementia, and death around age 50. Akinesia was prominent at a late stage, often with myoclonus. Grand mal seizures sometimes occurred, with occasional interictal spike and wave discharge; repetitive paroxystic periodic discharges were never recorded. A genealogical study, as far as possible free from line bias, has been conducted mainly by analysis of municipal records. 1 435 subjects in 10 generations, linked to affected subjects through ascent/descent or marriage, were listed in a computer file; the corresponding genealogical tree or selected part thereof are generated by computer. Application of Bayesian techniques to demographic data makes possible an estimation of disease probability in subjects for which no clinical data were available: such an estimate was confirmed by the later discovery of a living patient in descent of a subject with 0.7 estimated disease probability. No patient was found in descent from an inbred union known as such. Patients are the only transmitters. The sex ratio is not significantly different from 1. There is no detectable maternal effect. The segregation ratio, as calculated from extensively known sibships, lies in the range 0.65 to 0.89; the lower value itself is significatively higher than the 0.5 value expected in an autosomal dominant monogenic Mendelian transmission. An environment factor is ruled out by the diversity of locations and circumstances in kindred members. Such a kindred may represent an useful model for fundamental studies in Alzheimer's disease and senile dementia of the Alzheimer type.

Twenty-four clinically normal horses were castrated by routine methods. Peritoneal fluid was collected prior to castration and at 1, 3, 5, and 7 days postcastration. Peritoneal fluid was collected on days 9 and 11 if nucleated cell (NC) counts were still markedly elevated on day 7. Peritonitis, defined as NC counts greater than 10,000/microliters, was evident in 15 horses following castration. Mean NC counts peaked on day 5 but were less than 10,000/microliters for 74% of the horses by day 7, and 90% of the horses by day 9. One horse had a NC count greater than 60,000/microliters on day 11 when sampling ended. Postcastration peritoneal fluid was obviously blood-tinged in 21 horses. Peak RBC counts occurred on day 3 but markedly decreased by day 5. Elevated peritoneal RBC counts correlated well with elevated NC counts (P less than 0.001). Horses with peritonitis tended to have fever (P less than 0.05). Other clinical signs of peritonitis were not apparent.

Neurogenic bladder dysfunction, characterized by hesitancy, need to strain, decreased stream, and increased duration of urination, developed in 104 (63%) of 166 employees working in the manufacture of polyurethane foam. Highest rates of illness (69%) occurred in production workers, and no illness occurred in office or warehouse workers. Onset of the epidemic coincided with introduction of a catalyst, dimethylaminopropionitrile (DMAPN), and monthly case incidence rates increased as DMAPN use increased. Outbreak ceased abruptly when DMAPN use was stopped. Of eight patients who underwent neurourologic testing during recovery, seven lacked either detrusor reflex or normal sensation of bladder filling; seven had a subclinical sensory abnormality; three had prolonged sacral-evoked responses; and two of these three had limb motor neuropathies. Dimethylaminopropionitrile is unique among known neurotoxins in producing urinary symptoms more frequently than limb nerve symptoms.

Six-MP and its palladium and platinum complexes of this compound were administered intraperitoneally to 28 day old Sprague-Dawley rats in dosages of 15 mg/kg, 26.85 mg/kg, respectively for 21 days. The leukopenia induction capacity of 6-MP was greater at the end of day 7 while the 6-MP-Pd complex evidenced a more drastic leukocyte reduction at the end of day 21. The platinum complex was less toxic, as demonstrated by greater weight gain, while treatment with the palladium complex resulted in approximately the same weight gain as that observed in rats treated with pure 6-MP.

The combination of carbidopa and levodopa (Sinemet) is a highly effective treatment for the symptoms of Parkinson's disease. However, side effects, such as abnormal involuntary movements, fluctuations in motor performance, and "wearing off" phenomena limit its long-term usefulness in some patients. Open-label studies show that controlled-release Sinemet CR is effective in reducing motor fluctuations. This report discusses the results of a 14-week double-blind crossover study comparing the efficacy and tolerability of standard Sinemet with controlled-release Sinemet CR. Overall, there were no statistically significant differences in efficacy between Sinemet CR and standard Sinemet on any of the major efficacy measures, suggesting a clinical equivalence in terms of treating the symptoms of Parkinson's disease. The study also supports the tolerability of Sinemet CR. In summary, Sinemet CR holds the promise of reducing some disturbing side effects of long-term levodopa therapy, thus achieving optimal control of parkinsonian symptoms.

This chapter focuses on neurological conditions that may seriously change work performance or risk, as well as considerations in neurological evaluation of the asymptomatic worker.

Occupational exposures to neurotoxic chemicals have produced large outbreaks of illness in chemical and pesticide workers worldwide. Outbreaks of occupational neurologic disease in the United States have included (1) the Kepone episode in Hopewell, Virginia, in which 76 workers at a pesticide plant producing the chlorinated hydrocarbon insecticide, Kepone, developed a previously unrecognized syndrome of nervousness, tremor, ataxia, weight loss, opsoclonus, pleuritic and joint pain, and oligospermia; (2) an outbreak of 104 cases of autonomic neuropathy in polyurethane foam workers in Marblehead, Massachusetts, manifest principally by urinary bladder dysfunction, which followed exposure to a new catalyst, dimethylaminopropionitrile (DMAPN); and (3) an outbreak of acute mixed motor and sensory neuropathy in 48 plastic fabric workers in Columbus, Ohio, exposed to the solvent methyl butyl ketone (MBK). These outbreaks underscore the vulnerability of chemical workers to neurotoxins. In addition, occurrence of these large, easily detectable epidemics suggests that many more smaller clusters and single cases of neurologic disease of undetermined origin, particularly in younger adults, may be caused by exposure to occupational or to other toxic chemicals. Detection of the etiology of chemically induced neurologic illness requires a high index of suspicion and careful ascertainment of occupational history.

To the Editor.— Faden and Towsend, in the April issue of theArchives(33:278, 1976), consider myoclonus a confusing sign in early differential diagnosis of Alzheimer and Crutzfeld-Jakob diseases. They overlooked our own publication ( Neurology 13:811-823, 1963) in which we called attention to the association between myoclonus and Alzheimer disease. The observation of neurofibrillary tangles in the anterior horn cells in such cases suggests that the myoclonus may arise in the spinal cord, as well as in the cerebrum. In addition, the appearance of myoclonus probably depends on the rate of progression and eventual distribution of neuronal degeneration, rather than the disease process.