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Biomedical subjects

J Jankovic

Publications and source records attributed to J Jankovic.

At least 181 records · Page 10Linked to original sources

A screening method for occupational reproductive health risk.

Most currently recognized occupational exposure limits do not consider reproductive toxicological end points consistently when establishing recommended exposure limits. In many cases the information is not available, but perhaps as often, existing data is not employed. Further, many manufacturer's material safety data sheets omit reproductive hazard information. A method for identifying potential reproductive toxins and screening levels for associated health risks useful for hazard communication and exposure control is presented. To date, the Registry of Toxic Effects of Chemical Substances lists between 5000 and 6000 chemicals, drugs, and natural substances that show a positive outcome in at least 1 reproductive effects study. This reproductive health risk assessment began with these substances. Using elements of the Environmental Protection Agency's health risk assessment process, the list was reduced to 213 chemicals during the hazard identification step. Occupational reproductive guidelines (ORGs) were developed in the dose-response evaluation step. At the time of this writing, 85% of the chemicals identified in the hazard identification step have had a screening level dose-response assessment completed. Of these, 13% are greater than or equal to a threshold limit value (TLV). The remaining 87% do not have a TLV or ORGs below the TLV. The reproductive toxins list, along with the corresponding dose-response-derived ORGs that have been completed, appears at the end of the text.

Dose-Response Relationship, Drug↗

Cardiovascular and metabolic responses to upper- and lower-extremity exercise in men with idiopathic Parkinson's disease.

BACKGROUND AND PURPOSE: The aerobic capacity of individuals with Parkinson's disease (PD) has not been characterized. This study (1) compared maximal exercise performance in individuals with and without PD, (2) compared exercise performance during upper- and lower-extremity exercise, and (3) described submaximal exercise responses. SUBJECTS: Eight men with PD (PD group) and 7 men without PD (control group) participated. METHODS: Subjects performed a lower-extremity ergometer test (LE test) and an arm-cranking ergometer test (AC test). Peak oxygen consumption, heart rate, respiratory exchange ratio, and power, as well as submaximal values of oxygen consumption and heart rate for each power level, were recorded. RESULTS: No differences were found between the groups for either test. Peak power was less for the PD group than for the control group for both tests. Submaximal heart rate and oxygen consumption were higher for the PD group than for the control group. CONCLUSION AND DISCUSSION: We conclude that individuals with mild to moderate PD can be tested with both exercise protocols to a peak exercise capacity and that there are differences in upper- and lower-extremity peak power and submaximal responses between persons with and without PD.

Aged↗

Ecstasy intoxication: an overlap between serotonin syndrome and neuroleptic malignant syndrome.

3,4-Methylenedioxymethamphetamine (MDMA), also known as "ecstasy" is a popular recreational drug with potential for abuse. Although its neurotoxic effects have been established in animal studies, the acute and long-term effects of this serotonergic agent in humans are still unknown. We describe a 19-year-old woman with overlapping symptoms of neuroleptic malignant syndrome and serotonin syndrome after a single exposure to MDMA. We also review 15 other cases reported in the literature to draw attention to the serious neurotoxicity, including fatal outcomes, caused by the use of this increasingly popular, illicit drug.

Adolescent↗

Delayed-onset progressive movement disorders after static brain lesions.

We studied 53 patients (64% females) with static brain lesions who developed progressive movement disorders. Of these, 50 (94%) had dystonia, 17 (32%) tremor, eight (15%) parkinsonism, seven (13%) myoclonus, and three (6%) chorea. The precipitating insults included perinatal hypoxia/ischemia in 22 (42%), stroke in 12 (23%), head injury in eight (15%), encephalitis in eight (15%), and carbon monoxide poisoning, kernicterus, and radiation necrosis in one patient (2%) each. Among the 30 patients with initial insult occurring at age 2 years or younger (Infant group), distribution of dystonia at follow-up was focal in three (10%), segmental in eight (27%), unilateral in 10 (33%), and generalized in nine (30%). The mean latency between the original injury and onset of movement disorder was 25.5 +/- 16.7 years. Among the nine patients who developed dystonia after an insult occurring between ages 6 and 17 (Childhood group), the distribution of dystonia at follow-up was segmental in two (33%) and unilateral in seven (78%); the mean latency of dystonia onset was 4.9 +/- 7.8 years. Of the 14 patients in the Adult group (injury at age 25 or older), 11 developed dystonia, two developed parkinsonism, and one had carbon monoxide encephalopathy and parkinsonism. The distribution of dystonia in the 11 patients at follow-up was segmental in three (27%) and unilateral in eight (73%). The mean latency of movement disorder onset in the 14 patients of the Adult group was 2.5 +/- 4.9 years. No individuals in the Childhood or Adult groups became left-hand dominant; by comparison, nine of the 30 individuals in the Infant group became left-handed. In conclusion, brain injury at a young age is associated with a longer latency to onset of subsequent movement disorder, a greater tendency to development of generalized dystonia, and a greater probability of altered handedness. These tendencies may result from differences in age-related neuroplasticity.

Adult↗

Neuropsychological functioning in cortical-basal ganglionic degeneration: Differentiation from Alzheimer's disease.

Patients with cortical-basal ganglionic degeneration (CBGD) display prominent rigidity and apraxia, exhibit an asymmetric onset of symptoms, and may show other symptoms including abnormal saccadic eye movements, the "alien limb" sign, limb dystonia, and myoclonus. We compared the neuropsychological test performances of 21 CBGD patients with 21 Alzheimer's disease (AD) patients displaying no extrapyramidal symptoms and with 12 ADA patients who did show such symptoms. Groups were matched for age, educational level, and overall severity of dementia. Since the cognitive deficit was mild in most CBGD patients, most AD patients included in this study were also only mildly demented. The CBGD patients performed significantly better than the AD patients on test of immediate and delayed recall of verbal material; whereas the AD patients (with or without extrapyramidal symptoms) performed better on tests of praxis, finger tapping speed, and motor programming. The CBGD and AD groups all displayed prominent deficits on tests of sustained attention/mental control and verbal fluency, and exhibited mild deficits on confrontation naming. The CBGD patients endorsed significantly more depressive symptoms on the Geriatric Depression Scale.

Aged↗

Neurologic presentation of Wilson disease without Kayser-Fleischer rings.

A 41-year-old woman presented with a 6-month history of gradually progressive postural instability and dysarthria associated with cerebellar and extrapyramidal signs. No Kayser-Fleischer (K-F) rings were observed on biomicroscopic examination of each cornea. The only evidence of hepatic dysfunction was a modest elevation of alanine-aminotransferase. The diagnosis of Wilson disease (WD) was based on low serum ceruloplasmin, abnormal serum copper and urinary copper excretion, and DNA marker segregation analysis. WD should be considered in the presence of characteristic neurologic and laboratory features, regardless of age at onset, evidence of hepatic dysfunction, or absence of K-F rings.

Adult↗

Accuracy of clinical criteria for the diagnosis of progressive supranuclear palsy (Steele-Richardson-Olszewski syndrome).

We assessed the validity and interrater reliability of neurologists who, using four different sets of previously published criteria for the clinical diagnosis of progressive supranuclear palsy (PSP), also called Steele-Richardson-Olszewski syndrome, rated 105 autopsy-proven cases of PSP (n = 24), Lewy body disease (n = 29), corticobasal ganglionic degeneration (n = 10), postencephalitic parkinsonism (n = 7), multiple system atrophy (n = 16), Pick's disease (n = 7), and other parkinsonian or dementia disorders (n = 12). Cases were presented in random order to six neurologists. Information from each patient's first and last visits to the medical center supplying the case was presented sequentially to the rater, and the rater's diagnosis was compared with the neuropathologic diagnosis of each case. Interrater agreement for the diagnosis of PSP varied from substantial to near perfect, but none of the criteria had both high sensitivity and high predictive value. Because of these limitations, we used a logistic regression analysis to identify the variables from the data set that would best predict the diagnosis. This analysis identified vertical supranuclear palsy with downward gaze abnormalities and postural instability with unexplained falls as the best features for predicting the diagnosis. From the results of the regression analysis and the addition of exclusionary features, we propose optimal criteria for the clinical diagnosis of PSP.

Aged↗

A controlled trial of deprenyl in children with Tourette's syndrome and attention deficit hyperactivity disorder.

We conducted a double-blind placebo-controlled crossover study to assess the efficacy of deprenyl for attention deficit hyperactivity disorder (ADHD) in children and adolescents with comorbid Tourette's syndrome (TS). Twenty-four subjects (21 boys, 3 girls; mean age 12 years) were enrolled at two sites (University of Rochester and Baylor College of Medicine). The design included two 8-week treatment periods separated by a 6-week washout period. The primary outcome measures for ADHD and tic severity were total scores on the DuPaul Attention Deficit Hyperactivity Scale (DADHS) and the Yale Global Tic Severity Scale (YGTSS). Fifteen subjects completed the study. The primary analysis revealed no statistically significant beneficial effect of deprenyl on the DADHS (mean improvement 1.3; 95% CI, -2.7 to 5.3; p = 0.50). Further post-hoc analyses revealed, however, that the effect of deprenyl in the first period was substantial (p = 0.02). There was a marginally statistically significant beneficial effect of deprenyl on the YGTSS total score (p = 0.06). Deprenyl may improve both ADHD and tics in children with TS and warrants further study.

Adolescent↗

Clinical research criteria for the diagnosis of progressive supranuclear palsy (Steele-Richardson-Olszewski syndrome): report of the NINDS-SPSP international workshop.

To improve the specificity and sensitivity of the clinical diagnosis of progressive supranuclear palsy (PSP, Steele-Richardson-Olszewski syndrome), the National Institute of Neurological Disorders and Stroke (NINDS) and the Society for PSP, Inc. (SPSP) sponsored an international workshop to develop an accurate and universally accepted set of criteria for this disorder. The NINDS-SPSP criteria, which were formulated from an extensive review of the literature, comparison with other previously published sets of criteria, and the consensus of experts, were validated on a clinical data set from autopsy-confirmed cases of PSP. The criteria specify three degrees of diagnostic certainty: possible PSP, probable PSP, and definite PSP. Possible PSP requires the presence of a gradually progressive disorder with onset at age 40 or later, either vertical supranuclear gaze palsy or both slowing of vertical saccades and prominent postural instability with falls in the first year of onset, as well as no evidence of other diseases that could explain these features. Probable PSP requires vertical supranuclear gaze palsy, prominent postural instability, and falls in the first year of onset, as well as the other features of possible PSP. Definite PSP requires a history of probable or possible PSP and histopathologic evidence of typical PSP. Criteria that support the diagnosis of PSP, and that exclude diseases often confused with PSP, are presented. The criteria for probable PSP are highly specific, making them suitable for therapeutic, analytic epidemiologic, and biologic studies, but not very sensitive. The criteria for possible PSP are substantially sensitive, making them suitable for descriptive epidemiologic studies, but less specific. An appendix provides guidelines for diagnosing and monitoring clinical disability in PSP.

Humans↗

Restless legs syndrome: clinicoetiologic correlates.

Despite recent attempts to better characterize restless legs syndrome (RLS), this neurologic disorder remains poorly understood. The relationship between idiopathic and secondary and between familial and sporadic (nonfamilial) cases have not been previously defined. We studied 54 patients (29 women and 25 men) who satisfied the diagnostic criteria for RLS. The mean age of the patients was 62.69 +/- 13.82 years, and the mean age at onset was 34.13 +/- 20.30 years. We found that 92% of patients with idiopathic RLS (without neuropathy) had a family history of RLS, whereas only 13% of those with neuropathic RLS (associated with peripheral neuropathy) had a positive family history. The sporadic/neuropathic patients were older at symptom onset and tended to have a more rapid progression than the familial/idiopathic patients. There were no other significant differences between the subgroups. Levodopa and dopamine agonists were the most effective treatments. We conclude that there are two major etiologic subgroups of RLS but that the two share central pathophysiologic mechanisms.

Adult↗

Surgical treatment of Parkinson's disease.

Improved understanding of the pathophysiologic mechanisms underlying parkinsonian signs and symptoms, as well as refinement of methods and techniques in neurosurgery, neuroradiology and neurophysiology, have stimulated the current interest in and expanded the role of surgical treatment of Parkinson's disease. Pallidotomy and thalamotomy are the stereotactic procedures most commonly performed in patients who fall to obtain satisfactory relief of their symptoms despite optimal medical therapy. Small lesions disrupt the abnormal activity of basal ganglia circuitry. Other options currently being studied include chronic high-frequency stimulation and transplantation of fetal mesencephalic tissue. Chronic thalamic stimulation, involving permanent implantation of a deep brain electrode and a pulse generator, effectively controls contralateral tremor. Fetal nigral transplantation, which is still an experimental procedure, has the potential of restoring lost nigrostriatal pathway. The choice of treatment depends on the severity of the symptoms and their response, or lack of response, to pharmacologic therapy. With appropriate selection criteria, functional and symptomatic improvement can be achieved in most patients with Parkinson's disease who are treated with neurosurgical procedures. The long-term effects of these treatments, however, await the results of longitudinal studies.

Brain↗

Peripherally induced tremor and parkinsonism.

OBJECTIVE: Trauma to the peripheral nervous system is a well-recognized cause of dystonia and tremor, but peripherally induced parkinsonism has not previously been documented. We seek to characterize peripherally induced tremor and parkinsonism and propose possible mechanisms for this phenomenon. DESIGN: Review of records of patients evaluated in the Movement Disorders Clinic between 1977 and 1993. In addition to demographic and clinical information, the records were screened for any potential predisposing factors. PATIENTS: Twenty-eight patients in whom the onset of tremor, parkinsonism, or both was anatomically and temporally related to local injury. INTERVENTION: The type and site of injury were verified by history and examination of records whenever possible. Severity of tremor and parkinsonism was assessed by clinical rating scales. Three patients with tremor and parkinsonism had their striatal [18F]-fluorodopa uptake and raclopride binding measured with positron emission tomography. MAIN OUTCOME MEASURE: Response to conventional antitremor and antiparkinsonian medication was assessed by a clinical rating scale. RESULTS: Severe local injury preceded the onset of movement disorder by 47.5 +/- 74.7 days (mean +/- SD). The mean age at onset of movement disorder was 46.5 +/- 14.1 years. Tremor was present in all 28 patients, 11 of whom exhibited additional parkinsonian features. In 20 patients, the movement disorder spread beyond the original site. Possible predisposing factors were identified in 13 patients; nine had essential tremor or a family history of essential tremor. In addition to tremor, dystonia and myoclonus were evident in 13 and three patients, respectively. Reflex sympathetic dystrophy was present in six patients. Tremor did not improve with medications, and only seven patients with parkinsonism responded to therapy with levodopa. CONCLUSION: Central reorganization in response to peripheral injury may give rise to a motor disturbance, including tremor and parkinsonism.

Adult↗

Factors predictive of the need for levodopa therapy in early, untreated Parkinson's disease. The Parkinson Study Group.

OBJECTIVE: To identify characteristics of patients with early, untreated Parkinson's disease that are the most important predictors of rapid functional decline. DESIGN: Prospective observational study of a cohort of 800 patients with early, untreated Parkinson's disease who were involved in a multicenter, randomized, double-blind, controlled clinical trial of selegiline hydrochloride (L-deprenyl) and vitamin E (alpha-tocopherol). PRIMARY OUTCOME VARIABLE: Time from randomization to the onset of disability that necessitated levodopa therapy (end point), as judged by the enrolling investigator. METHODS: Stepwise Cox regression was used in combination with clinical judgment to identify the most important independent baseline predictors of the primary end point among a host of variables, including treatment with selegiline and vitamin E, global and specific clinical measures of disease severity, demographic variables, and neuropsychological test results. RESULTS: In addition to selegiline treatment and global disease severity measures, such as the stage according to the criteria of Hoehn and Yahr, impaired domestic capacity, and the activities of daily living score, the complex of postural instability/gait difficulty and bradykinesia were found to be the factors that were most highly associated with the risk of reaching the end point. CONCLUSIONS: The findings suggest that patients with Parkinson's disease whose early clinical presentation includes either postural instability/gait difficulty or bradykinesia are at high risk for rapid functional decline.

Adult↗

Paroxysmal dyskinesias: clinical features and classification.

We studied 46 patients with paroxysmal dyskinesia and classified them according to phenomenology, duration of attacks, and etiology. There were 13 patients, 7 females, who had paroxysmal kinesigenic dyskinesia (PKD), 10 with attacks lasting 5 minutes or less (short lasting) and 3 with attacks lasting longer than 5 minutes (long lasting). Twenty-six patients, 18 females, had paroxysmal nonkinesigenic dyskinesia (PNKD), 9 with short-lasting and 17 with long-lasting PNKD. Five patients, 3 females, had paroxysmal exertion-induced dyskinesia (PED), 3 with short-lasting PED and the other 2 with long-lasting PED. In addition, there was 1 patient with paroxysmal hypnogenic dyskinesia (PHD) and 1 with paroxysmal superior oblique myokymia. Only 2 patients, 1 with PKD and 1 with PHD, had family history of paroxysmal dyskinesias. No specific cause could be identified in 21 patients; in the other 23 patients the etiologies included the following: psychogenic (9 patients), cerebrovascular diseases (4), multiple sclerosis (2), encephalitis (2), cerebral trauma (2), peripheral trauma (2), migraine (1), and kernicterus (1). Nine of 10 (90%) patients with PKD improved with medications, mostly anticonvulsants, compared with only 7 of 19 (37%) with PNKD. This new classification, based chiefly on precipitating events, allowed appropriate categorization of the attacks in all our patients with paroxysmal dyskinesias.

Adolescent↗

Tourettism associated with Huntington's disease.

The identification of the gene for Huntington's disease (HD) has made it possible to diagnose patients with HD who present with unusual or atypical features. We describe a 41-year-old man whose initial manifestation of HD was dominated by the presence of motor and vocal tics and other features of Tourette's syndrome. This case illustrates the broad range of clinical manifestation of HD and the usefulness of testing for the HD mutation in selected cases with familial movement disorders.

Adult↗