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Although exercise and physical therapy are commonly recommended to patients with Parkinson's disease (PD), their utility has seldom been objectively validated. In order to determine parameters that might be used in a prospective study of rehabilitation therapy in PD, we reviewed the in-hospital courses of forty-five PD patients admitted to our inpatient PD rehabilitation service between 1987and 1989. The mean length of stay was about one month. Patients' functional performances were evaluated according to a standard protocol at admission, periodically during their stay, and again prior to discharge by both physical and occupational therapists and by the nursing staff. Despite the fact that the average daily dose of anti-Parkinsonian medication did not change over the course of the stay, improvements were noted in patients' abilities to ambulate and to transfer, as well as in dressing and personal hygiene. Timed tests proved less sensitive measures than did estimations or the amounts of assistance patients...

In neurologic rehabilitation nothing is currently in clinical use that is effective in restoring lost neurologic function. This paper presents an overview of the various medicines that have been studied for their potential to facilitate recovery after brain injury. Early studies of acetylcholine and anticholinesterase drugs were reported favorably, but subsequent experience with them has not substantiated the initial enthusiasm. In the last two decades, data from work on rodents and cats suggest that certain drugs may facilitate or impede neurologic recovery after brain injury. Human studies on the effects of d-amphetamine and related compounds are sparse, and, although provocative, several problems make the results controversial. Data from studies in the laboratory suggest that clinicians may be impeding clinical outcome in stroke patients with some frequently used poststroke medications. A table lists (with references) the drugs that may impede recovery or reinstate deficits and drugs that may accelerate recovery.

35 Parkinson's disease patients with motor response fluctuations (RF) participated in controlled clinical trials comparing Sinemet CR to Standard Sinemet (STD) at our institutions. 13 of 25 eligible patients continued to two years (the longest possible follow-up from the second study), and 5 of 11 have continued taking CR up to 4 years. At the end of both two and four years, patients were taking significantly fewer medication doses, with a significantly longer interdose interval, and up to two years, experienced fewer "off" periods than when on Standard Sinemet (STD) alone. Most patients required STD at at least one dose each day to hasten to onset of antiparkinson effect. Sinemet CR is a useful adjunct in the long-term management of motor response fluctuations in Parkinson's disease.

Baclofen, a centrally acting gamma-aminobutyric acid agonist is a commonly used pharmacotherapy for spasticity of spinal origin. It is primarily excreted by glomerular filtration with a clearance proportional to creatinine clearance. We describe a 39-year-old quadriplegic women who, over a 16-week period, developed clinical signs of baclofen toxicity confirmed by progressively rising serum baclofen levels while on a conventional stable dosing regimen. During this period blood urea nitrogen and creatinine concentrations were normal and stable (9mg/dL and 0.8mg/dL, respectively). However, creatinine clearance values were consistently low (55 to 60m/min), suggesting renal insufficiency as the underlying cause. After a decrease in baclofen dosage, evidence of baclofen toxicity resolved. Clinicians should be alert to signs of evolving baclofen toxicity even in patients on an apparently stable regimen. Baclofen dosage adjustments based on systemic baclofen level may play a role in optimizing the clinical management of spasticity.

The decline in stroke mortality, increased longevi­ ty, and modest increases in the incidence of stroke result in more individuals living with physical dis­ ability caused by cerebrovascular disease. This is creating an increasing burden on the facilities and expertise of individuals who are concerned with the rehabilitation of the patient after stroke. The costs of rehabilitation services are considerable, and there is concern about the cost-effectiveness of rehabilitative care for pat ients with stroke. Not every individual following a stroke is a candi­ date for rehabilitative therapy. A number of investi­ gations have been conducted as to who is most likely to benefit from stroke rehabilitation. Third-party reimbursers in the United States have made determi­ nations on this issue and have set guidehnes for ad­ missioncriteria for inpatient rehabihtation. Admission criteria include that the patient must (a) be medically stable, (b) be responsive to verbal or visual stimuli, (c) have sufficient mental alertness to participate in a program, and (d) have a condition that indicates a potential for rehabilitation with a reasonable expecta­ tion of improvement. The patient must be able to enter a program that requires at least 3 h of active participation per day in physical therapy, occupa­ tional therapy, speech therapy, or rehabilitation nursing. A number of attempts have been made to deter­ mine from the large population of patientswithstroke which ones might be the best candidates for rehabil­ itation. Assuming a population of 100 patients follow­ ing an ischemic cerebral infarction 14 days after the ons et of stroke, approximately 14% of the patients will be dead, 13% will be normal, 20% will have hemi­ plegia, 49% will have hemiparesis, and 4% will have monoparesis. Thus, 73% of the total are potential candidates for inpatient rehabilitation. Analyzing this group of 73 patients, approximately 18-24 will be too well to need inpatient rehabilitation and 18-24 will be too neurologically impaired or medically unstable to be able to enter a rehabilitation program, leaving approximately one-quarter to one-third of the total group as good candidates for rehabilitation.

Publisher Summary This chapter provides an overview of the rehabilitation of a patient after a stroke. Stroke is the most common cause of disability and reason for rehabilitation in individuals over 60. The highly variable outcome of stroke from any cause generally governs the need for rehabilitation programs. Rehabilitation for patients with stroke should begin immediately after the development of physical disability that does not rapidly recover. Paresis or paralysis of one side of the body is the most common reason for rehabilitation. The type of stroke usually does not affect the need for rehabilitation, because the degree of physical disability is the main feature in deciding the need. In the acute care hospital, rehabilitation generally involves preventive measures which should be routine to avoid later complications. These include the muscle contracture due to immobile extremities and joints, pressure sores, and shoulder injury with the “shoulder–hand syndrome.” The effects of rehabilitation are greatly influenced by the severity of the neurologic deficit and whether there is natural recovery. Correlating the severity of the neurological deficit with the ability to ambulate with and without assistance and ability to achieve a Barthel score gives a good indication of the chances of becoming independent.

My association with Stroke began in 1969, when the idea of a new American Heart Association (AHA) journal to be devoted to stroke was first proposed. The idea of a new journal went through the extensive review of doubts that it was necessary and concern for its survival. There were at the time 2 well-established American journals and 2 British journals publishing articles related to neurological diseases. The usual questions arose of why another journal, and why not send relevant articles on stroke to the existing ones. There were a number of things that indicated that a journal solely devoted to work on stroke would be successful. There had been 6 Princeton Conferences on stroke since 1954, and it was believed that these conferences had stimulated increased interest in stroke. Also, the Stroke Council of the AHA was creating increasing interest in stroke and what could be done about it. Interest was in addition stimulated by establishing a separate heart association meeting on stroke that began during my chairmanship of the council. The resulting research work stimulated by these activities was believed to provide a rich source of material that could easily support a new journal. With the interest and urging provided by Clark Millikan and Irving Wright, the AHA was persuaded to begin a new journal. Clark Millikan became the first editor. My association with the journal began when I was asked to become an associate editor in 1971, which I accepted with enthusiasm. Editorship of AHA journals was generally limited to 5 years, but this was extended for 2 years …

We reviewed the histories of patients seen in a large Parkinson's disease clinic from 1983 to 1989 to determine if there is a relationship between the timing of initiation of levodopa therapy and the development of motor response fluctuations, dyskinesias, and dementia. There were no factors predisposing to the development of response fluctuations or dementia. Younger age at disease onset predisposed to the development of dyskinesia. Dyskinesias occurred in a greater proportion of patients in whom the initiation of levodopa therapy was delayed by more than 2 years from disease diagnosis than among those in whom treatment was started earlier. We thus failed to identify any adverse consequences of early levodopa treatment in our patient population.

• Glutethimide has been used to control essential tremor. Its efficacy in the treatment of disabling cerebellar and rubral tremor was assessed in an open study of six patients with multiple sclerosis and two patients with traumatic brain injury. Functional and quantitative tremor severity was assessed before treatment and 7 to 14 days after a stable dose was achieved. Six of eight patients exhibited visible functional benefit from treatment with glutethimide; abstract testing results correlated well with functional status in most cases. Four patients chose to continue to receive medication. Controlled trials of glutethimide to compare its efficacy with that of other medications used in the treatment of action tremor are indicated.

We conducted disability and mortality studies to determine if the male preponderance usually found in Parkinson's disease (PD) was reflected in different courses of the diseases in the 2 sexes. We analyzed longitudinal disability score in 47 men and 23 women with PD followed for 6 years at UCLA. We found no significant differences between the sexes in mean disability scores in any of the 6 years. Mean dopa dosage was significantly higher in men, possibly reflecting their generally larger body mass. Choreoathetosis, dementia, or other side effects did not differ between the 2 groups. We obtained observed to expected mortality ratios in 239 men and 132 women followed for 3,831 person-years from records of 4 medical centers. Using the sex-specific US Life Tables to calculate expected mortality, we found the observed to expected ratio for the men was 1.7457 and for the women 2.4740, a significantly greater excess in female mortality. Analyses of mortality using tables which are not sex-specific will fail to uncover the decreased longevity in women with PD. We conclude that, despite the male preponderance in PD, men and women acquire it at the same age, have the same progression and duration of disease, and die at the same age; whereas, in the general population, women have a longer life expectancy than men. It is not known what factors protect women from incurring PD and what lowers their life expectancy to that of men when they do have the disease.

A day care program for patients with dementia was developed by the Burke Rehabilitation Center in 1979. Sixty-nine patients have taken part in the program, some for as long as three years. The majority of patients stay in the program for one to two years. This pilot program was designed to provide a structured series of daily activities for the patient with dementia and to give those responsible for their care at home a period of freedom each week from the responsibilities of care. The program has been well received by the patients and appreciated by their families. It has not altered the steady progression of intellectual decline. It has made it possible for families to continue to keep patients at home and delay nursing placement or the hiring of additional help at home. It is cost effective when compared with the general alternative of nursing home placement. Similar programs could be conducted outside health care facilities at lower cost to patients and their families. Family support group discussions have eased the burden for the caregiver and have been useful in discovering new ideas for better patient management.

With a computerized data base, a data retrieval system, and a computer program using the actuarial method of life-table analysis, we compared survival rates in different subgroups of patients with dementia of the Alzheimer type (DAT; n = 199). Men (n = 71) had a shorter duration of survival than women (n = 128), with 500-day survival (mean +/- SEM) 84 +/- 5% vs. 99 +/- 3%, p less than 0.01; 1000-day survival 49 +/- 10% vs. 96 +/- 8%, p less than 0.001; 50% survival 1000 days vs. 1550 days. Patients younger than 65 years at onset had a decreased relative duration of survival compared with patients over 65 at onset, suggesting a more malignant course. Patients with a longer duration of illness tended to die sooner, but this effect was not statistically significant. The Kahn-Goldfarb mental-status quotient was not a predictor of survival. Patients with high Haycox behavioral score (greater than 20; n = 50), indicating more severe behavioral impairment, had lower survival rates at 500 days than patients with low scores (less than 12; n = 65) (80 +/- 6% vs. 95 +/- 3%, p less than 0.05). Hachinski ischemic score, measuring signs and symptoms of vascular disease, had no correlation with survival. Factors associated with decreased duration of survival in DAT include male sex, presenile onset, and increased severity of behavioral impairment.

Experience at the Burke Rehabilitation Center indicates that a rehabilitation program established early and giving proper attention to both personal and medical aspects can make it possible for 80% of stroke victims to return home and to function with reasonable adequacy. Rehabilitation efforts should begin as soon as possible after a stroke and can be effectively carried out in community hospitals.

Five patients with advanced Parkinson's disease and fluctuations in therapeutic response to levodopa participated in, and four completed, an open label study of the efficacy of Sinemet CR5. Reductions in the number of daily doses and "off" periods as well as the increase in interdose interval and percent "on" time versus standard Sinemet were comparable to those achieved with Sinemet CR4 in these same patients. As compared with Sinemet CR4, there was a greater delay in the occurrence of peak plasma levodopa concentrations, and relative bioavailability was reduced. Sinemet CR5 appears to offer no advantages over Sinemet CR4 in the treatment of response fluctuations in Parkinson's disease.

Irregularities in motor response after continuing levodopa therapy of Parkinson disease (the "on-off effect") were assessed with the addition of L-alpha-methyldopa hydrazine (carbidopa) in a double-blind study. Thirteen of 20 patients improved while receiving carbidopa and levodopa while only four of 17 patients improved while receiving placebo and levodopa. Twenty-three of 37 patients improved in a subsequent non-blind trial of carbidopa plus levodopa. Improvement was not dependent on an increase in dose or frequency of levodopa administration. Adverse effects included dyskinesia, imbalance, and confusion; nausea was eliminated. On patient died of glomerulonephritis that predated the drug trial, but worsened progressively during and after it. Carbidopa's suppression of the "on-off effect" suggests that extracerbral factors may be important in this phenomenon.

Introduction Diphenylhydantoin is one of the most frequently used anticonvulsants, and it has a relatively low incidence of serious side reactions. The common signs of dose-related toxicity are nystagmus, ataxia, dysarthria, and drowsiness. Diphenylhydantoin must usually be given to adults in amounts of 500 mg or more a day1to produce clinical evidence of intoxication. Buchthal et al2reported that mild toxic symptoms and signs were observed with blood levels of 15μg/ml, and severe symptoms and signs have been noted with diphenylhydantoin blood levels of 30μg/ml or more. However, this report does not give a detailed account of the relationship of the specific symptoms and signs of toxicity to diphenylhydantoin blood levels. Along with our studies of toxicity and defects in the metabolism of diphenylhydantoin, detailed data have been obtained relating symptoms and signs of toxicity to blood levels of diphenylhydantoin. The first part of this paper deals

The problems involved in measuring improvement as well as the conceptual difficulties in considering this phenomenon were considered in general terms. Data on 300 patients with nonembolic cerebral infarction followed from five to nine years are presented, indicating that improvement in function of a paralyzed extremity may occur in the early phase after stroke but was extremely unlikely to continue during long-term follow-up from three months to five years. It was concluded that improvement in function might be determined more by retraining of the nonaffected muscles and particularly of the unaffected side rather than by recovery of the area paralyzed.

In 1968 the Council on Cerebrovascular Disease of the American Heart Association authorized the appointment of a subcommittee to produce a statement concerning "risk factors for Stroke." After working for over a year the Subcommittee reported that, because of inadequate data concerning "all or several of the factors," they had been unable to produce a statement satisfactory to each Subcommittee member. Some were reluctant to set down a policy statement until every loophole was plugged--a task made extraordinarily difficult by the complexity of Stroke and the fact that prospective studies of large population groups are necessary for the acquisition of some needed data. Another problem was that of interpreting the phrase risk factors. Does this phrase imply that eliminating or minimizing a "risk factor" (for example, maintaining successful control of hypertension) automatically reduces the risk of Stroke for that individual? This therapeutic consideration may await an answer for years, although it must be admitted that the term "risk factors for Stroke" does suggest that careful treatment of one or several risk factors can help to prevent Stroke. In any event, the Subcommittee was admonished by its chairman, Dr. William Kannel, to consider the task a never-ending one; that data are now available indicating that certain phenomena are more commonly followed by Stroke and that these phenomena (culprits) should be publicly identified as elements or risk factors for Stroke. The Subcommittee decided to work first with the profile of the candidate at risk of a cerebral infarction--and so state. The Subcommittee realistically writes: "Any statement arrived at will be subject to periodic revision as more information is accumulated!" Obviously, new data may make changes necessary! Under Dr. Kannel's talented and dedicated leadership the Subcommittee produced the statement which follows.

The frequency of occurrence of nonembolic cerebral infarction is linearly related to age. The sexual frequency of nonembolic cerebral infarction is directly related to the age group of the sample studied. The mortality of nonembolic cerebral infarction and its prognosis are most closely related to the age of the patient at the time of stroke. The older the patient, the higher is the mortality and the poorer the prognosis. The cause of death in nonembolic cerebral infarction is as much a function of age-related concurrent diseases, especially cardiac disease, as it is of stroke itself. The natural history of stroke is more related to the natural history of cardiac disease than it is to cerebral vascular disease. These data may be viewed as lending support to the thesis that nonembolic cerebral infarction and the diseases that are frequently found with it, such as diabetes, cardiac disease and hypertension, are related in their occurrence and mortality to aging and may truly be concurrent events and not etiologically related one to the other.

A double blind study was carried out in which patients with atherosclerotic cerebrovascular disease and cerebral infarction were randomly selected for treatment with 1.25 mg Premarin or placebo. No prophylactic effect in preventing the recurrence of cerebrovascular accidents or myocardial infarctions could be demonstrated when patients were followed from 6 months to 3 yr. The data from this study suggests that Premarin in this dosage, 1.25 mg, may have a harmful effect as the treated patients in general fared less well than the controls.

Quantitative and semiquantitative methods have been used to evaluate the clinical improvement of 62 patients with completed stroke who were admitted to a rehabilitation hospital. Improvement in motility and leg strength on the paretic side was minimal and was not influenced by facilitation exercise techniques. Observed changes in strength and motility occurred to about the same degree on both the nonparetic and paretic sides. Patients who had a short interval between onset of stroke and admission to the rehabilitation program improved significantly more on the paretic side than those with a longer interval. Practically no improvement in motility and leg strength was found two months following a stroke. Hemiplegia and hemiparesis were defined quantitatively on the basis of motility test scores. Patients with hemiparesis showed greater improvement in motility and self-care status in about half the time of hospital stay when compared with patients with hemiplegia. In spite of relatively static neurological deficits, all patients showed evidence of functional improvement as assessed by a self-care rating scale. The poorest functional outcome was seen in patients who had hemisensory losses in addition to hemiplegia. The observations indicate that early, functionally oriented stroke rehabilitation programs offer the best chance of aiding patients. Behavioral and sociological influences on final outcome are important and must be carefully evaluated to insure maximum chances of successes in rehabilitation.

Penicillin G, 20 million units daily given intravenously to a nonuremic patient, caused encephalopathy (progressive restlessness, confusion, hallucinations, and multifocal myoclonus) followed by recovery after discontinuation of the drug. In normal awake cats doses up to 1.3 million units/ kg produced encephalopathy with myoclonus; higher doses culminated in status epilepticus and death. Pretreatment with small doses minimized the effects of a subsequent high dose. In awake rats 4.5 to 5 million units/kg produced encephalopathy resulting in death of the majority of animals. In rats anesthetized with ether, same results were obtained with 3 to 3.5 million units/kg. The highest concentrations of labeled penicillin G in brain, located mostly in membranal-nuclear fraction, was reached in five to ten minutes. The penicillin encephalopathy was reversed in animals by intravenously administered penicillinase.

The bluish-black spots of lipid-containing materials stained with a saturated solution of Sudan black B in 55% ethanol were found to fade and change color to brownish-pink shades in 5 min if exposed to ultraviolet light. Spots that were exposed to daylight for 6 hr on a sunny day lost 14% of their original color intensity but the decrease was less on cloudy days. Exposure to H2S initiated fading and color change in 2 hr. Exposure to HCl vapors restored the original color but not its intensity. Spots kept in darkness and wrapped airtight showed a decline of 2.5% in color intensity after 96 hr and no obvious color change. The speed and extent of change of color and fading of the various fractions of the dye separated by means of paper chromatography were different. Heat coagulated serum proteins were stained blue with commercial Sudan black B solution in 55% ethanol.

IT IS well accepted today that the prevalence of diseases caused by microorganisms is altered by climatic fluctuations. The increased incidence of pulmonary infection [l] in the winter and of poliomyelitis and gastro-intestinal infections in the summer are the best examples of this and probably reflect a combination of variations in (1) the host’s susceptibilities; (2) bacterial or viral virulence; and (3) vector availability. Stroke should not have a seasonal variation unless the major causative factors underlying its precipitation, including for instance atherosclerosis and circulatory dynamics, are modified by climate and season. Such factors as eating and drinking habits vary with the temperature; summer dehydration may alter circulatory dynamics and lead to cerebral infarction. There are suggestions of a seasonal variation in cholesterol levels in a stable population of men aged 46-62. Cholesterol levels were found to be highest from November to March and lowest during the summer months, May through August [2, 31. In a similar study involving both sexes, males and females showed seasonal variations of cholesterol levels in opposite directions [4]. Protein bound iodine levels have been found to vary seasonally, the lowest values found during June, July and August with high values in September, October, February and March [4]. The gap between these suggestions of seasonal variation in serum cholesterol and PBI and the occurrence of stroke is too wide for any meaningful connection. Some evidence for a seasonal variation in atherosclerotic disease is found in studies of coronary heart disease. Death from cardiovascular disease in some parts of the United States has a peak during December to April with a low point in August and September [6, 71. The reduction of death rates during the summer months has been confirmed in studies in areas with a marked seasonal climatic variation but not in areas which are continuously warm [S]. In Australia cardiovascular deaths are higher during their winter months, June through September, and lowest during their summer months, January through April [9]. In the field of cerebrovascular disease Takakashi in Japan found that cerebral hemorrhage had a low incidence in the summer months, June to September, and a high incidence in the winter months [IO].

Radio-opaque contrast media interfered with the normal process of fibrin and plasma clot formation. The morphologic changes included a decrease of the fibrin fiber diameter and an increase of protein aggregates. These appeared amorphous in the light microscope and showed a linear relationship with the concentration of contrast agents in the reaction mixture. Above a threshold concentration, which was different for each contrast media, no clot formed. With increasing concentrations of contrast medium between 3.5 x 10-3M and 2.0 x 10-2M, the optical density of the clots decreased rapidly while the incorporation of fibrin monomers into the polymer structure of the clots stayed within normal limits. This indicated that the spatial arrangements of the clots was altered. Electron micrographs confirmed that the fibrin fibers were reduced by 70 per cent to 90 per cent of the control fiber diameter in the presence of 6.1 x 10-2M sodium diatrizoate. The fibrin stabilizing enzyme (FSF, LLF or Factor XIII) catalyzed covalent cross links despite the structural changes in the clot.

THERE have been few studies of the incidence and prognosis of seizures in patients with nonembolic cerebral infarction. Jackson in 18641was amongst the first to comment upon a relationship between seizures and vascular disease, particularly embolic cerebrovascular occlusion, but he had no pathological confirmation of his diagnosis. Gowers in 18812collected and reported 66 patients with "hemiplegia" and epilepsy, in some of whom the hemiplegia was thought to have resulted from embolic cerebrovascular occlusion. Two thirds of his patients were less than 5 years of age, and pathological confirmation of the specific cause of "hemiplegia" was not obtained. Dunham in 19163reported seven patients with epileptic seizures found in a group of 100 patients consecutively admitted because of cerebrovascular accidents. The group was composed of patients with cerebrovascular disease of all sorts, and the fact that four of the seven epileptics also had syphilis

A study of the coagulation parameters of 87 normal controls (ages 50 to 80) were compared with those of 33 patients with thrombotic stroke and 55 patients with diabetes mellitus of the same age distribution. There were no significant differences when tested for the influence of sex or age. Twenty-seven tests of clotting were done on each specimen, a total of 4,725. Significant differences were detected between normals versus patients with thrombotic stroke (fibrinogen level, glass clotting time, silicone clotting time, heparin tolerance, platelet count and retarded thromboplastin generation time BaSO 4 1:50 dilution) and between normals versus patients with diabetes (prothrombin time, silicone clotting time, platelet count, thromboplastin generation time and retarded thromboplastin generation time) when subjected to computer analysis. The clinical significance of these differences is not of practical value in the diagnosis or as a guide to therapy for stroke.

Saturated solutions of commercial Sudan II, III and IV in 60% ethanol were found to stain heat-coagulated fat-free purified human serum albumin and defatted whole serum. The protein staining components were isolated and identified by means of paper chromatography on mineral oil-impregnated filter paper with 95% ethanol as the developing agent. The brownish and yellowish fractions which migrated rapidly in this system stained proteins well, whereas the red, pink and orange fractions, which migrated slowly, stained lipids only. The solubility and staining power of the slowly migrating lipid coloring fractions remained satisfactory in absence of the rapidly moving protein staining fractions.

• To investigate further the role of growth hormone (GH) on the cerebral effects of levodopa, human somatotropin (human growth hormone) was administered to four patients with parkinsonism with varying response to chronic levodopa therapy. The doses of somatotropin (5 IU) were administered on alternate days for four days, and the effects of this hormone on the patient's symptomatic control, dyskinesia, plasma GH, and dopa levels were evaluated and compared with those of patients receiving saline injections. We have demonstrated that administration of exogenous human somatotropin, even during marked and sustained elevations of plasma GH levels, does not alter the therapeutic or side effects of levodopa therapy. With one exception, plasma dopa levels after human somatotropin administration remained unchanged. We conclude that neither the endogenous increases of GH in response to levodopa nor those attained following human somatotropin administration modify in any consistent way the therapeutic and side effects of chronic levodopa therapy, and that the episodic releases of GH in response to levodopa occur independently of its cerebral effects.

Piribedil, a dopamine agonist, was administered to 13 patients with long-standing Parkinson9s disease whose major symptoms were not well controlled on levodopa, anticholinergics, alpha-methyldopa, amantadine, or a combination of these agents. Twelve of the 13 clearly benefited from the addition of Piribedil although side effects precluded long term use in two cases. Beneficial results were obtained by using a combination of Piribedil, levodopa, and anticholinergic drugs. Side effects (hallucinations, confusion, dyskinesias) were frequent, but were usually reversible by lowering the dosage of levodopa or the accompanying anticholinergic medication. The synergistic effect of Piribedil and other antiparkinsonian drugs emphasizes the need for careful titration of all available medications in difficult cases and demonstrates the usefulness of dopamine receptor stimulators when drugs acting presynaptically have failed.

Symptoms and signs of postural instability are often present in patients with Parkinson disease (PD). Because vestibular dysfunction might contribute to the postural instability, we carried out bithermal caloric tests and electronystagmography in 36 patients with PD and 316 controls. Significantly more PD patients had reduced and absent vestibular responses than controls. Decreased or absent vestibular responses in patients with PD were associated with postural instability and increasing severity of other symptoms. Vestibular dysfunction may contribute to the postural instability of PD.

We examined longitudinal disability scores in 54 patients with Parkinson's disease followed for 6 years at UCLA. We sorted data into 3 groups based on age at onset of symptoms: group A, onset under 50 years; group B, 50 to 59 years; group C, 60 years or older. There were no significant differences between groups initially. All 3 groups improved dramatically when levodopa was given, but group A showed significantly less disability in years 4, 5, and 6 than did group C. The groups did not differ with respect to side effects. To determine if age at onset affected mortality, we sorted records from 4 geographically diverse centers into the same 3 groups. Results on 359 patients followed for 3,314 person-years, covering a period of 17 years after onset of symptoms, showed that group A had the most favorable observed-to-expected mortality ratio, 1.82, compared with 2.17 and 2.20 for groups B and C respectively, but the difference was not statistically significant. Results from the disability analyses indicate that patients with onset of Parkinson's disease under 50 years of age may have a more favorable prognosis than those whose symptoms begin in later years.

R ehabilitation efforts following stroke are provided by a number of clinical specialists: rehabilitation nurses, physical therapists, occupational therapists. speech therapists, social workers, and physicians. The concept of a stroke rehabilitation team has developed as a means of focusing these diverse backgrounds on the specific needs of individual patients. It is reasonable to expect some documentation of the benefit of such a therapistintensive rehabilitation program. The most easily validated rehabilitation techniques consist of bracing and use of ambulation assist devices. Fitting patients with an ankle brace and giving them a cane does not assure that they will walk or that if they do they will do so safely. Patients require instruction in proper sequencing of the cane and hemiplegic leg plus time and practice to incorporate these devices into automatic movements. Once the patient has learned to use these devices, their efficacy can be easily demonstrated by taking them away

• The dexamethasone suppression test (DST) result was found to be abnormal in 49% of patients who were an average of seven weeks post stroke. The DST response correlated with depressive symptoms as measured by both the Zung and modified Hamilton Depression scales. The specificity of the DST for clinically diagnosed depression reached 87% for the 8 am cortisol determination, with a corresponding sensitivity of 47%. It was not related to the patient's final level of self-care function as measured by the Barthel score, need for nursing home placement following discharge, or duration of rehabilitation needed to achieve maximum benefit. Abnormal responses were more prevalent in cerebral hemisphere than in brain-stem or cerebellar strokes. The more extensive the stroke the more likely the possibility of an abnormal DST response. The DST response is stable, with test-retest replicability being 84% at two weeks and 74% at seven weeks.

The role of specific risk factors for Alzheimer’s disease (AD) is undefined. We compared medical histories in 259 patients with clinically diagnosed AD with those in cognitively intact patients (CI;n=36). The two groups were comparable in age (mean±SEM 73.3±0.6 in AD, 70.9 ±2.1 in CI), race (>95% white), and socioeconomic status, although they differed in male:female ratio (1:2 in AD; 1.6:1 in CI). Stroke was more common in CI (11.1% vs 1.5%, p=.006), presumably because demented patients with stroke tend to be diagnosed as multi-infarct dementia rather than AD. Family history for dementia was positive in 35.9% of AD patients, but only 5.6% of CI patients (p

The neuroendocrine properties and the beneficial effects of cyproheptadine in tardive dyskinesia led to the testing of this drug in levodopa-induced dyskinesia. Cyproheptadine administered to 6 parkinsonian patients in doses of up to 42 mg/day was of no significant benefit in either dyskinesia or symptom control. Improvement in appetite was reported by 3 patients. These observations suggested that different mechanisms may be responsible in the pathogenesis of phenothiazine and amine-induced dyskinesia. The failure to control levodopa-induced dyskinesia selectively with serotonin agonists and antagonists and the accentuation of the dyskinesia in the presence of anticholinergic agents further suggest that substances that increase directly central cholinergic activity may be effective in the control of levodopa-induced dyskinesia.

Propranolol treatment of patients with essential tremor, selected for chronic, nonresting tremor of hands and head causing functional impairment, benefited only one of nine patients during a double-blind study (320 mg per day). No serious cardiorespiratory complications occurred in this screened patient group, but an elderly man became agitated and depressed. We conclude that propranolol does not benefit all patients with essential tremor and that this disorder may be caused by several biochemical mechanisms.