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Biomedical subjects

J Jankovic

Publications and source records attributed to J Jankovic.

At least 109 records · Page 6Linked to original sources
PubMed2000

Use of botulinum toxin type A in the treatment of cervical dystonia.

Botulinum toxin is the most neurotoxic substance known, with a specific action at cholinergic synapses. Acting as a zinc endopeptidase, botulinum toxin cleaves specific proteins involved in vesicle fusion, thereby preventing release of acetylcholine. The therapeutic effect of the toxin taken up presynaptically at the neuromuscular junction is to weaken muscle. Botulinum toxin type A (BTX-A) has been shown to be safe and effective in the treatment of cervical dystonia (CD; also known as spasmodic torticollis). In patients with CD, injections of botulinum toxin dampen or eliminate involuntary muscle activity and improve control of neck movement, pain, and range of motion. To successfully use botulinum toxin as a therapeutic modality, targeting the dystonic muscles, injecting a sufficient quantity of toxin and minimizing diffusion into uninvolved muscle collectively provide the best outcome with the fewest adverse reactions. EMG guidance may allow more precise injections. To maintain responsiveness to the toxin over repeated injections, using the lowest dose at the longest dosing interval has been suggested.

Dystonia↗
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↗
PubMed1999

New and emerging therapies for Parkinson disease.

Few neurological disorders have been more successful in introducing novel therapies than Parkinson disease (PD). However, despite enormous progress, many challenges remain. Although levodopa is still the most effective drug in the symptomatic treatment of PD, adverse effects, particularly motor fluctuations and dyskinesias, limit its usefulness. Furthermore, there is a growing concern about the escalating cost of PD treatment: the cost-benefit aspect of the novel approaches must be balanced against the advantages of long-term experience with established treatments.

Dopamine Agonists↗
PubMed1999

Movement and reaction times and fine coordination tasks following pallidotomy.

The effect of a unilateral, microelectrode-guided lesion in the globus pallidum internum (GPi) was evaluated in 41 patients (21 women) with moderately advanced Parkinson's disease (PD). The mean age was 60.3+/-9.0 years (range, 40-74) and the mean symptom duration was 14.7+/-5.3 years (range, 4-25). In addition to clinical ratings, movement time (MT) and reaction time (RT) tests were performed at baseline and 3 months after surgery during the "practically defined off" state (more than 12 hours after the last dose of levodopa). Improvement occurred bilaterally with more robust and statistically significant improvement on the contralateral side in all RT tests. Simple reaction time (SRT) improved by 14.5% (p<0.001) and the choice reaction time (CRT) by 12.2% (p<0.001) when the arm contralateral to the pallidotomy side was tested. There was a trend toward improvement in the ipsilateral arm. The MT, determined by repetitive movement between two adjacent targets, improved by 24% contralaterally (p<0.0001) and by 12% ipsilaterally (p<0.005). In addition, the Purdue Pegboard (PP) test scores, used to evaluate hand dexterity, improved on the contralateral side by 35.5% (p<0.0002) but there was no statistically significant ipsilateral improvement. To the extent that MT and RT are quantitative measures of bradykinesia, our study provides evidence that this parkinsonian feature improves after pallidotomy.

Adult↗
PubMed1999

Bilateral hemifacial spasm: a report of five cases and a literature review.

We describe five patients with bilateral hemifacial spasm evaluated in a Movement Disorders Clinic to illustrate the clinical characteristics and to draw attention to the differential diagnosis of this condition. All patients had unilateral onset followed by bilateral, asymmetric, and asynchronous facial contractions. The mean age of the patients (4 women and 1 man) was 70.6 years (range, 54-81 yrs), and the mean duration of symptoms was 17 years (range, 2-30 yrs). The facial twitching started in the left eyelid in all cases and the opposite side of the face began to twitch on the average 8.4 years (range, 0.2-15 yrs) later. Imaging studies revealed tortuous vertebrobasilar arteries in three patients. Four patients were successfully treated with botulinum toxin injections. Bilateral hemifacial spasm is a rare, peripherally induced disorder that must be differentiated from tics, dystonia including blepharospasm and other cranial dystonia, and other facial dyskinesias. Botulinum toxin injection appears to be the treatment of choice.

Aged↗
PubMed1999

A novel sublingual apomorphine treatment for patients with fluctuating Parkinson's disease.

We tested a novel preparation of a sublingual apomorphine hydrochloride tablet (APO) in 10 patients with advanced Parkinson's disease complicated by motor fluctuations. After a dose titration, patients took either 40 mg APO three times per day alternating with levodopa doses (eight patients) or six doses of 20 mg APO taken concurrently with levodopa doses (two patients) for 3 months. Assessments included timed tapping and ambulation tests, Unified Parkinson's Disease Rating Scale (UPDRS), and patient diaries. Tapping speed while taking only APO (12 hours after stopping levodopa) was faster than while taking only levodopa (p <0.05). The daily levodopa dose decreased by 32.1% (p <0.01), yet the total "on" time increased from 73.5% +/- 10.2% to 81.5% +/- 7.5% of the day (p <0.01) after starting APO. "On" UPDRS part II scores (p <0.05) and "on" UPDRS part III (motor examination) scores (p <0.05) also improved. Adverse events such as nausea, orthostatic hypotension, and disagreeable taste did not limit the dose of APO in any case. The short-term benefit and tolerability demonstrated in this study warrant further study of this new APO preparation.

Administration, Sublingual↗
PubMed1999

Selective agenesis of mesencephalic dopaminergic neurons in Nurr1-deficient mice.

Nurr1, a member of the nuclear receptor superfamily of transcription factors, has been found to be essential for the development of ventral midbrain dopamine (DA)ergic neurons. To study the regional selectivity and phenotypic specificity of regulation by Nurr1 of the genesis of DAergic neurons, we examined DAergic, serotonin (5-HT)ergic, norepinephrine (NE)ergic, cholinergic, glutamate (GLU)ergic, and gamma-aminobutyric acid (GABA)ergic neurons in the brains of Nurr1-deficient mice by immunohistochemistry and biochemistry. We demonstrated that in homozygous Nurr1-deficient mice (Nurr1-/-), DAergic neurons were totally absent in substantia nigra and ventral tegmental area, but preserved in other regions including diencephalon and hypothalamus, olfactory bulb (OB). Levels of DA in Nurr1-/- mice were decreased by 98% in striatum (Str) and 65% in OB. NEergic neurons in locus ceruleus, 5-HTergic neurons in raphe nuclei, and cholinergic neurons in basal forebrain and other regions were not changed. A 30% reduction of NE was found in the Str of Nurr1-/- mice. The levels of GLU and GABA and the activity of choline acetyl transferase in the brains of Nurr1-/- mice were not significantly altered. Our results demonstrate a selective and specific deficit of DA and absence of DAergic neurons in the mesencephalic structures of Nurr1-deficient mice, which resembles the pattern similar to that seen in patients with Parkinson's disease (PD). This model may contribute to our understanding of the mechanisms influencing DAergic cell survival in PD.

Animals↗
PubMed1999

Clinical features differentiating patients with postmortem confirmed progressive supranuclear palsy and corticobasal degeneration.

Progressive supranuclear palsy (PSP) and cortocobasal degeneration (CBD) are often clinically confused with each other because they share a rapid disease progression, parkinsonism that responds poorly or transiently to levodopa therapy, and associated signs (e.g., ocular abnormalities, pyramidal signs and cognitive involvement). To improve the accuracy in diagnosing these disorders, this study examined the clinical features of 51 patients pathologically diagnosed with PSP and CBD. Logistic regression analysis identified two sets of predictors (models) for CBD patients, one consisting of asymmetric parkinsonism, cognitive disturbances at onset and instability and falls at first clinic visit, and the other one of asymmetric parkinsonism, cognitive disturbances at symptom onset and speech disturbances. While PSP patients often had severe postural instability at onset, symmetric parkinsonism, vertical supranuclear gaze palsy, speech and frontal lobe-type features, CBD patients presented with lateralized motor (e.g., parkinsonism, dystonia or myoclonus) and cognitive signs (e.g., ideomotor apraxia, aphasia or alien limb). On the other hand, CBD patients presenting with an alternate phenotype characterized by early severe frontal dementia and bilateral parkinsonism were generally misdiagnosed. PSP patients without vertical supranuclear gaze palsy were misdiagnosed. Recognizing the features which differentiate these disorders and the less obvious disease presentations as well as developing an increased index of suspicion will improve the diagnostic accuracy of these disorders.

Aged↗
PubMed1999

Neuroprotection by pramipexole against dopamine- and levodopa-induced cytotoxicity.

Pramipexole, a novel non-ergoline dopamine (DA) agonist, has been applied successfully for treatment of Parkinson's disease (PD). We report here that pramipexole can protect dopaminergic cell line Mes23.5 against dopamine- and levodopa-induced cytotoxicity possibly through a mechanism related to antioxidant activity. In the MES 23.5 cultures, DA and L-DOPA induce a dose- and time-dependent cytotoxicity, as determined by tetrazolium salt and trypan blue assays. Furthermore, an in situ terminal deoxynucleotidyl transferase assay demonstrates that DA-induced cell death is apoptotic. Pretreatment with pramipexole in a concentration range (4-100 microM) significantly attenuates DA- or L-DOPA-induced cytotoxicity and apoptosis, an action which is not blocked by D3 antagonist U-99194 A or D2 antagonist raclopride. Pramipexole also protects MES 23.5 cells from hydrogen peroxide-induced cytotoxicity in a dose-dependent manner. In cell-free system, pramipexole can effectively inhibit the formation of melanin, an end product resulting from DA or L-DOPA oxidation. These results indicate that pramipexole exerts its neuroprotective effect possibly through a mechanism, which is independent of DA receptors but related to antioxidation or scavenging of free radicals (e.g. hydrogen peroxide). As a direct DA agonist and potentially neuroprotective agent, pramipexole remains attractive in the treatment of PD.

Animals↗
PubMed1999

Bruxism and cranial-cervical dystonia: is there a relationship?

To characterize the relationship between bruxism and dystonia, 79 patients (28 men and 51 women) with cranial-cervical dystonia were studied. Sixty-two patients (78.5%), 22 men and 40 women, had bruxism. The mean age at onset of dystonia in patients with bruxism was 52.4 +/- 12.6 years (range 14-80), similar to patients with cranial-cervical dystonia without bruxism. Involuntary oromandibular movements (46 patients) and blepharospasm (34 patients) were the most common initial symptoms among patients with dystonia. About one-fourth of bruxism patients had associated dental problems including TMD (21%) and tooth wear (5%). A majority (58%) of the bruxism patients had diurnal bruxism and 12% had nocturnal bruxism. The bruxism patients were compared to 100 patients with Parkinson's disease (PD), cervical dystonia, cranial dystonia, and normal controls, respectively. The prevalence of bruxism was much higher in the cranial-cervical dystonia patients when compared to normal controls (P < 0.001); however, this difference was not significant between other diseased groups and controls. Medications and botulinum toxin injections, used in the treatment of focal dystonia also provided effective relief of bruxism.

Adolescent↗