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J Jankovic

Publications and source records attributed to J Jankovic.

At least 19 recordsLinked to original sources
PubMed2000

Polymorphism of NACP-Rep1 in Parkinson's disease: an etiologic link with essential tremor?

An allele (263bp) of the nonamyloid component of plaques (NACP)-Repl polymorphism has shown association with sporadic PD in a German population. The authors studied this polymorphism in 100 American PD patients and 100 healthy controls. The authors also studied 46 essential tremor (ET) and 55 Huntington's disease (HD) patients. Allele 263bp was significantly higher in PD patients (OR = 3.86) and ET patients (OR = 6.42) but not HD patients, compared with healthy controls. The association of allele 263bp with PD and ET suggests a possible etiologic link between these two conditions.

Adult↗
PubMed2000

Pramipexole inhibits lipid peroxidation and reduces injury in the substantia nigra induced by the dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine in C57BL/6 mice.

Pramipexole has been showed to protect cultured dopaminergic (DAergic) cells against free radical-induced cytotoxicity. To test if pramipexole is protective against 1-methyl-4-phenyl-1,2,3, 6-tetrahydropyridine (MPTP)-mediated nigral DAergic injury in vivo and if such protection is related to inhibition of lipid peroxidation, DAergic function and lipid peroxidation were determined in MPTP-treated C57BL/6 mice. We reported that MPTP administration induced a 38.1% increase of lipid peroxidation product thiobarbituric acid reactive substance (TBARS) in nigra, a 46.7% decrease of tyrosine hydroxylase -positive nigral DAergic neurons and a 59.4% reduction of striatal DA levels. However, pramipexole treatment significantly inhibited the TBARS production by 76%, and attenuated the MPTP-induced decreases in nigral DAergic neurons and striatal DA levels by about 50%. This study suggests that pramipexole can inhibit free radical-mediated lipid peroxidation and protect MPTP-induced nigral injury.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed2000

The evolution of diagnosis in early Parkinson disease. Parkinson Study Group.

CONTEXT: Since there is no diagnostic biological marker for Parkinson disease (PD), the diagnosis is based on the results of clinical assessment. The accuracy of diagnosis improves with time and repeated assessments. Studies that require only inclusion of early cases of PD present a diagnostic challenge. Previous studies concluded that initial diagnoses of PD made by general neurologists were incorrect in 24% to 35% of the cases when patients were examined at autopsy. Experts in movement disorders are expected to have greater accuracy of initial diagnosis of PD. OBJECTIVE: To determine the evolution of clinical diagnosis in patients with early PD made initially by experts in PD. DESIGN: Eight hundred patients with mild parkinsonian symptoms (Hoehn and Yahr stage 1 or 2) who received a diagnosis of PD less than 5 years before the beginning of the study were included in the original Deprenyl and Tocopherol Antioxidative Therapy for Parkinson's Disease study. These patients were followed up prospectively with repeated clinical assessments. The following clinical criteria were used to reassess the initial diagnosis: investigator's confidence in the diagnosis of PD, presence of atypical clinical features, findings of imaging studies, response to levodopa, and results of autopsy examinations. RESULTS: The mean +/- SD duration of illness in the 800 cases at enrollment was 2.2+/-1.3 years, and the mean +/- SD Hoehn and Yahr stage was 1.6+/-0.5. The mean +/- SD follow-up was 6.0+/-1.4 years (range, 0.2-7.6 years). In 5 cases, PD was not confirmed at autopsy, and in 15 patients, the results of imaging studies indicated the presence of other pathological conditions. Of the 550 cases treated with levodopa, 49 (8.9%) had little or no improvement; 6 of these cases overlap with either autopsy or imaging study exclusion criteria. Two other cases had at least 4 of the 6 atypical clinical features arguing against the diagnosis of PD. Thus, of the 800 patients, 65 (8.1%) did not have PD according to the study criteria. Compared with those patients with the final diagnosis of PD, in the diagnoses of 60 patients without autopsy, the duration of symptoms (mean +/- SD, 7.2+/-2.0 years vs. 8.3+/-1.9 years; P<.001) and the duration of follow-up (5.3+/-1.6 years vs. 6.1+/-1.3 years; P<.001) were shorter. CONCLUSIONS: We found that 65 (8.1%) of patients initially diagnosed as having PD were later found to have an alternate diagnosis based on multifactorial clinical diagnostic criteria. This alternate diagnosis indicated that experts in PD changed their diagnoses infrequently during the 7.6-year follow-up.

Age of Onset↗
PubMed2000

Weight gain following unilateral pallidotomy in Parkinson's disease.

OBJECTIVE: To determine the clinical correlates and infer pathogenesis of weight gain following pallidotomy in patients with Parkinson's disease (PD). BACKGROUND: Surgical ablation of the globus pallidus internus (GPi) improves levodopa induced dyskinesias, moderately improves most other "cardinal" manifestations of PD, and has been noted to result in increased weight. METHODS: We incorporated Unified Parkinson's Disease Rating Scales (UPDRS) subscales, the Beck depression inventory and feeding questionnaire data into a linear regression model in order to determine which post-surgical change(s) may lead to weight gain over the first year following pallidotomy, n = 60. RESULTS: The mean weight gain 1 year after pallidotomy was 4.0 +/- 4.1 kg. Improvement in "off" motor scores (P < 0.005), especially gait subscores (P<0.0001), and to a lesser extent improvement in "on" motor scores (P<0.05) predicted weight gain. Changes in dyskinesia ratings, mood, food intake, dysphagia, levodopa dose, weight loss in the year prior to pallidotomy, age, and duration of PD did not correlate with subsequent weight gain. CONCLUSION: The high correlation between post-pallidotomy weight gain and "off" motor scores, suggests that this phenomenon is related to some change in underlying homeostasis associated with changes in the cardinal manifestations of PD itself, rather than secondary changes resultant from the surgery.

Dyskinesia, Drug-Induced↗
PubMed2000

Tardive and idiopathic oromandibular dystonia: a clinical comparison.

OBJECTIVE: Most patients with tardive dystonia have a focal onset involving the cranial-cervical region. Because of its resemblance to idiopathic cranial dystonia, a common form of dystonia, it often poses a diagnostic problem. To compare clinical features and response to botulinum toxin (BTX) injections between patients with tardive and idiopathic oromandibular dystonia (OMD). METHODS: Patients seen in a movement disorder clinic who satisfied the inclusion criteria for tardive or idiopathic OMD were studied. The clinical variables and responses to BTX between the two groups of patients were compared. In the tardive group, we also compared the clinical variables between those with oro-facial-lingual stereotypies, and those without. RESULTS: Twenty four patients with tardive OMD and 92 with idiopathic OMD were studied. There were no differences in the demographic characteristics. Most were women, with duration of symptoms longer than 8 years. The mean duration of neuroleptic exposure was 7.1 (SD 7.9) years. Jaw closure was the most frequent subtype of OMD (tardive=41.7%, idiopathic=51.1%). Idiopathic patients were more likely to have coexistent cervical dystonia (p<0.05), whereas isolated OMD was significantly higher in tardive patients (p<0.05). Limb stereotypies, akathisia, and respiratory dyskinesia were seen only in the tardive OMD. Frequency of oro-facial-lingual stereotypy was significantly higher in the tardive than the idiopathic group (75.0% v 31.5%, p<0.0001). The peak effect of BTX was similar in both groups. CONCLUSIONS: Oro-facial-lingual stereotypies were significantly more frequent in the tardive than the idiopathic group. Presence of stereotypic movements in the limbs, akathisia, and respiratory dyskinesias in patients with OMD strongly suggests prior neuroleptic exposure. Dystonia in tardive OMD is more likely to be restricted to the oromandibular region, whereas in patients with idiopathic OMD, there is often coexistent cervical dystonia. BTX is equally effective in both groups of patients.

Adult↗
PubMed2000

Treating severe bruxism with botulinum toxin.

BACKGROUND: Locally administered botulinum toxin, or BTX, is an effective treatment for various movement disorders. Its usefulness in treating bruxism, however, has not been systematically evaluated. SUBJECTS AND METHODS: The authors studied 18 subjects with severe bruxism and whose mean duration of symptoms was 14.8 +/- 10.0 years (range three-40 years). These subjects audibly ground their teeth and experienced tooth wear and difficulty speaking, swallowing or chewing. Medical or dental procedures had failed to alleviate their symptoms. The authors administered a total of 241 injections of BTX type A, or BTX A, in the subjects' masseter muscles during 123 treatment visits. The mean dose of the BTX A was 61.7 +/- 11.1 mouse units, or MU (range 25-100 MU), per side for the masseter muscles. RESULTS: The mean total duration of response was 19.1 +/- 17.0 weeks (range six-78 weeks), and the mean peak effect on a scale of 0 to 4, in which 4 is equal to total abolishment of grinding, was 3.4 +/- 0.9. Only one subject (5.6 percent) reported having experienced dysphagia with BTX A. CONCLUSION: The results of this study suggest that BTX administered by skilled practitioners is a safe and effective treatment for people with severe bruxism, particularly those with associated movement disorders. It should be considered only for those patients refractory to conventional therapy. Future placebo-controlled studies may be useful in further evaluating the potential of BTX in the treatment of bruxism.

Adolescent↗
PubMed2000

Dystonia in corticobasal degeneration.

Although a referral bias may have resulted in a higher proportion of atypical cases and consequently an overestimation of dystonia, asymmetric limb dystonia particularly affecting one arm initially was observed in 92% of all our CBD cases. Predominant leg dystonia is uncommon, and head, neck, or axial dystonia is rare. Dystonia is often associated with myoclonus, rigidity, apraxia, alien hand phenomenon, and sensory cortical signs in the affected limb, and there are no significant differences between the occurrence of these or other features, between patients with or without dystonia. There is no effective treatment for this relentless disorder except for temporary relief of dystonia and pain with local botulinum toxin injections. Further clinicopathologic studies are needed to elucidate the anatomical and physiologic substrates of dystonia in this disorder.

Basal Ganglia Diseases↗
PubMed1999

Botulinum toxin A in patients with oromandibular dystonia: long-term follow-up.

OBJECTIVE: To study the safety and efficacy of botulinum toxin A (BTX) in patients with oromandibular dystonia (OMD) and to compare the treatment results of the various subtypes of OMD. BACKGROUND: OMD is one of the most challenging forms of dystonia to treat. Pharmacologic therapies are generally not effective, and there are no surgical alternatives. METHODS: Of 202 patients diagnosed clinically to have OMD in a movement disorders clinic over a period of 10 years, 162 patients satisfied the study inclusion criteria. The masseters and submentalis complex were the only two muscle groups injected with BTX in this group of patients. RESULTS: The mean age was 57.9+/-15.3 years and the mean follow-up period was 4.4+/-3.8 years. More than half the patients had jaw-closing (JC) dystonia. A total of 2,529 BTX treatments were administered into the masseter muscles, submentalis complex, or both during a total of 1,213 treatment visits. The mean doses of BTX (per side) were 54.2+/-15.2 U for the masseters and 28.6+/-16.7 U for the submentalis complex. The mean total duration of response was 16.4+/-7.1 weeks. The mean global effect of BTX was 3.1+/-1.0 (range, 0 to 4, where 4 equals the complete abolition of the dystonia), with the JC dystonia patients responding best. Fifty-one patients (31.5%) reported adverse effects with BTX in at least one visit. Complications such as dysphagia and dysarthria were reported in 135 (11.1%) of all treatment visits. CONCLUSIONS: BTX is a safe and effective long-term treatment for OMD. JC dystonia responds better than jaw-opening or mixed dystonias, and the treatment of the latter types of OMD are more likely associated with dysphagia and dysarthria. Jaw-opening dystonia can be treated successfully by injecting the submentalis complex.

Adolescent↗
PubMed1999

Safety and efficacy of NeuroBloc (botulinum toxin type B) in type A-resistant cervical dystonia.

OBJECTIVE: To determine the safety and efficacy of botulinum toxin type B (BoNT/B) in patients with type A-resistant cervical dystonia (CD). BACKGROUND: Local intramuscular injections of BoNT are an effective therapy for CD. After repeated use, some patients become resistant to therapy. BoNT/B, effective in type A toxin-responsive patients, is proposed as an alternative therapy for type A-resistant patients. METHODS: The authors performed a 16-week, double-blind, placebo-controlled trial of BoNT/B in type A-resistant patients with CD. After resistance to therapy was confirmed with the frontalis-type A test, placebo or 10,000 U BoNT/B was administered in a single session into two to four clinically involved muscles. The Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) was the primary efficacy measurement. TWSTRS-Total, three visual analog scales (Patient Global Assessment of Change, Principal Investigator Global Assessment of Change, Patient Analog Pain Assessment), and adverse events were assessed at baseline and weeks 2, 4, 8, 12, and 16. RESULTS: A total of 77 patients participated (38 placebo, 39 active). Improvements in severity, disability, and pain were documented in the BoNT/B-treated group. TWSTRS-Total scores were improved in the BoNT/B-treated group at weeks 4 (p = 0.0001), 8 (p = 0.0002), and 12 (p = 0.0129). All three visual analog scales demonstrated improvements at week 4 (p < 0.0001, 0.0001, and 0.001). A Kaplan-Meier analysis supported a duration of effect of 12 to 16 weeks in the active group. Dry mouth and dysphagia were self-limited adverse effects, reported more commonly in the BoNT/B group. CONCLUSIONS: Botulinum toxin type B (BoNT/B) (NeuroBloc) is safe and efficacious for the management of patients with type A-resistant cervical dystonia with an estimated duration of treatment effect of 12 to 16 weeks.

Adult↗
PubMed1999

Bilineal transmission in Tourette syndrome.

OBJECTIVE: To investigate the frequency and pattern of bilineal transmission in families of patients with Tourette syndrome (TS) compared with normal control subjects. METHODS: The study population consisted of two groups: 1) consecutive patients with TS with both parents (51 family sets; 153 individuals), and 2) normal control subjects randomly selected from public schools (20 family sets; 60 individuals). All patients with TS, normal control subjects, and their parents were evaluated for evidence of TS and associated features. Structured interviews and detailed questionnaires designed to assess tics, obsessive-compulsive behavior (OCB), and attention deficit disorder (ADD) were administered to all people in both groups. RESULTS: In addition to tics, 43 (84.3%) patients with TS had ADD, 33 (64.7%) had OCB, and 31 (60.8%) had both ADD and OCB. In 42 (82.4%) of the 51 patients, at least one parent exhibited features of TS; unilineal transmission (only one parent with tics, OCB, or ADD) was present in 29 (56.9%) TS families and an additional 13 (25.5%) TS families manifested evidence of bilineal transmission (both parents affected). More fathers than mothers of patients with TS had tics (31.4% versus 15.7%), whereas more mothers had OCB than did fathers (33.3% versus 15.7%). Features of ADD were equally distributed among fathers (35.3%) and mothers (33.3%) of patients with TS. Eight of 1,142 (0.7%) children in the general school population had some evidence of TS. One of 40 parents of the normal control subjects (2.5%) had symptoms of ADD, but none of the parents of normal control subjects manifested any features of TS or OCB. CONCLUSIONS: This study found evidence for bilineal transmission in one fourth of TS families. Features of the TS spectrum were rare in normal control families. Evidence of tics, OCB, and ADD should be investigated in both parents of patients with TS.

Adolescent↗
PubMed1999

Levodopa-induced dyskinesias treated by pallidotomy.

Pallidotomy has been reported to improve parkinsonian symptoms, but its effects on levodopa-induced dyskinesia (LID) have not been thoroughly examined. We describe here the results of stereotactic, unilateral, posteroventral pallidotomy on LID in 42 patients (22 women), who were followed for up to 9 months. Their mean age was 60. 6+/-9.3 (range: 40-74), age at onset was 46.1+/-9.1 (range: 24-46), and duration of symptoms was 14.5+/-5.3 (range: 4-25) years. Three months following pallidotomy, the percent time with dyskinesia decreased from 37.0 to 17.3 (P<0.0001) and the percent time the patients were 'on' with dyskinesias decreased even more, from 71.0 to 22.9 (P<0.0001). Furthermore, the number of patients with troublesome (moderate to violent) dyskinesia had decreased from 36 (86%) prior to surgery to only 5 (12%) after surgery. The mean unified Parkinson disease rating scale (UPDRS) scores for LID-related disability and pain decreased from 1.95 to 0.74 (P<0. 0001) and from 1.02 to 0.17 (P<0.0001), respectively. Since the pre- and post-pallidotomy daily levodopa dosage remained essentially the same, the improvement in LID could not be attributed to a reduction in levodopa. Surgery-related complications occurred in eight (19%) patients, but none of them had persistent disability as a result of these complications. We conclude that pallidotomy is an effective and safe procedure in the treatment of medically intractable LID.

Adult↗
PubMed1999

Multiple system atrophy: the putative causative role of environmental toxins.

BACKGROUND: Whereas a number of studies have investigated the putative role of environmental toxins in the pathogenesis of idiopathic Parkinson disease, the possibility of such a role in multiple system atrophy has received little attention. DESIGN AND SETTING: Review of records of patients examined in the Parkinson's Disease Center and Movement Disorder Clinic, Baylor College of Medicine, Houston, Tex, from July 1, 1977, to February 4, 1998. PATIENTS: We reviewed 100 consecutive medical records of patients who satisfied the diagnostic criteria for multiple system atrophy formulated by the Consensus Committee of the American Autonomic Society and the American Academy of Neurology. INTERVENTION: The type and amount of toxin exposure were verified by history and examination of records whenever possible. Severity of parkinsonism was assessed by clinical rating scales. MAIN OUTCOME MEASURE: Development of multiple system atrophy after environmental toxin exposure. RESULTS: Eleven patients had a notable history of heavy exposure to environmental toxins. One patient with multiple system atrophy confirmed by postmortem evaluation was exposed to high concentrations of malathion, diazinon, and formaldehyde, while the other patients with multiple system atrophy had well-documented high exposures to agents including n-hexane, benzene, methyl isobutyl ketone, and pesticides. The case studied pathologically demonstrated extensive advanced glial changes, including glial cytoplasmic inclusions in deep cerebellar white matter, brainstem, cortex (superior frontal, insula) and putamen, with notable cell loss and depigmentation of the substantia nigra and locus ceruleus. CONCLUSION: While many studies report a possible role of environmental toxins in Parkinson disease, such a role is even more likely in multiple system atrophy, as this is a sporadic disease.

Environmental Pollutants↗
PubMed1999

Clinical correlates of vascular parkinsonism.

BACKGROUND: Parkinsonism may be due to other causes besides Parkinson disease (PD). Vascular parkinsonism (VP) has not been well defined and the clinical correlates of VP have not been clarified. OBJECTIVES: To seek evidence for or against the role of cerebrovascular disease in parkinsonism, and to identify clinical features that suggest a vascular origin. DESIGN: Retrospective chart review of patients with parkinsonism. A vascular rating scale was used to identify 2 patient groups, 1 with strong evidence of cerebrovascular disease (VP), and 1 with idiopathic PD. Clinical features of parkinsonism were then compared between the 2 patient groups. SETTING: A Movement Disorders Clinic, Baylor College of Medicine, Houston, Tex, a tertiary referral center. PATIENTS: Three hundred forty-six patients, 69 with VP and 277 with PD. RESULTS: The VP and PD groups were clearly differentiated in terms of evidence of cerebrovascular disease (P<.001 to P<.00001). Patients with VP were older, more likely to present with gait difficulty rather than tremor, and less likely to respond to the use of levodopa compared with patients with PD (P<.00001). Patients with VP were also significantly more likely to have predominant lower body involvement, postural instability, a history of falling, dementia, corticospinal findings, incontinence (P<.00001), and pseudobulbar effect (P<.05). CONCLUSIONS: These differences in clinical features suggest a different pathogenesis of parkinsonism in these 2 patient groups. The strong evidence of cerebrovascular disease in the VP group and the differences in clinical features support the concept of VP as a distinct clinical entity. We conclude that compared with PD, patients with parkinsonism associated with vascular disease are more likely to present with gait difficulty and postural instability rather than tremor, have a history of stroke and risk factors for stroke, and fail to respond to levodopa therapy.

Aged↗
PubMed1999

Effects of cerebrospinal fluid from patients with Parkinson disease on dopaminergic cells.

BACKGROUND: The pathogenesis of substantia nigra pars compacta neuronal injury in Parkinson disease (PD) remains unknown. Cerebrospinal fluid (CSF) has been reported to contain factors toxic to dopaminergic neurons. OBJECTIVES: To determine whether the cytotoxic effects of CSF of PD patients are specific for dopaminergic neurons, dependent on prior levodopa therapy, and mediated by the cytokine tumor necrosis factor alpha (TNF-alpha). DESIGN: Specimens of CSF were evaluated in dopaminergic (MES 23.5) and nondopaminergic (N18TG2) cell lines for cytotoxicity by viability assay and by the inhibition of tyrosine hydroxylase. After specificity and time and dose response were established, CSF specimens were assayed in a blinded manner. The TNF-alpha levels in CSF were determined by enzyme-linked immunosorbent assay. The toxicity of TNF-alpha in MES 23.5 cells was determined. SETTING: A university-based research facility. SUBJECTS: There were 4 groups of subjects: normal control subjects (n = 10), control subjects with neurologic disease (n = 8), PD patients treated with levodopa (n = 10), and untreated subjects with PD (n= 20). RESULTS: Specimens of CSF from 15 (50%) of 30 PD patients and 2 (11%) of 18 control subjects were cytotoxic to dopaminergic MES 23.5 cells and were nontoxic to the parental cell line N18TG2. There was no correlation between the degree of PD CSF cytotoxicity, levodopa therapy, or the severity and duration of PD. Terminal deoxynucleotidyl transferase-mediated biotin-deoxyuridine triphosphate nick-end labeling (TUNEL) for DNA fragmentation suggested the involvement of apoptotic mechanisms. The inhibition of tyrosine hydroxylase was an early effect of cell injury by PD CSF and correlated with the viability assay. The mean TNF-alpha level was 2.6-fold higher in CSF specimens from PD patients than in those of controls. The addition of recombinant human TNF-alpha equivalent to the highest level determined in PD CSF was not cytotoxic to MES 23.5 cultures. CONCLUSIONS: Blinded CSF specimens from PD patients, regardless of therapy, contain factors that cause specific dopaminergic neuronal cell injury. These factors are present in a substantial proportion of CSF specimens from patients with early PD, before the institution of medical therapy. Levels of TNF-alpha are elevated in the CSF of PD patients, but TNF-alpha is not responsible for the cytotoxicity.

Aged↗