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Joseph Jankovic

Publications and source records attributed to Joseph Jankovic.

126 records · Page 7Linked to original sources
PubMed2002

Secondary paroxysmal dyskinesias.

Paroxysmal dyskinesias (PxDs) are involuntary, episodic movements that include paroxysmal kinesigenic (PKD), paroxysmal nonkinesigenic (PNKD), and paroxysmal hypnogenic (PHD) varieties. Although most PxDs are primary (idiopathic or genetic), we found 17 of our 76 patients with PxD (22%) to have an identifiable cause for their PxD (10 men; mean age, 41.4 years). Causes included peripheral trauma (in three patients), vascular lesions (in four), central trauma (in four), kernicterus (in two), multiple sclerosis (in one), cytomegalovirus encephalitis (in one), meningovascular syphilis (in one), and migraine (in one). The latency from insult to symptom onset ranged from days (trauma) to 18 years (kernicterus), with a mean of 3 years. Nine patients had PNKD, two had PKD, five had mixed PKD/PNKD, and one had PHD. Hemidystonia was the most common expression of the paroxysmal movement disorder, present in 11 patients. Both of the patients with PKD had symptom durations of <5 minutes. Symptom duration ranged from 10 seconds to 15 days for PNKD and from 5 minutes to 45 minutes for mixed PKD/PNKD. There were no uniformly effective therapies, but anticonvulsant drugs, clonazepam, and botulinum toxin injections were the most beneficial. Awareness of the variable phenomenology and the spectrum of causes associated with secondary PxD will allow for more timely diagnosis and early intervention.

Adolescent↗
PubMed2002

Tourettism and dystonia after subcortical stroke.

The term "tourettism" has been used to describe Tourette syndrome (TS)-like symptoms secondary to some specific cause. Tics associated with attention deficit hyperactivity disorder (ADHD), obsessive-compulsive disorder (OCD), or both, are commonly present in TS, but this constellation of symptoms has been rarely attributed to stroke. We describe two boys who suffered a subcortical stroke and subsequently developed hemidystonia, tics, and behavioral comorbidities. Both had right hemispheric stroke involving the basal ganglia at 8 years of age, and in both the latency from the stroke to the onset of left hemidystonia was 2 weeks. In addition to ADHD and OCD, both exhibited cranial-cervical motor tics but no phonic tics. The temporal relationship between the stroke and subsequent TS-like symptoms, as well as the absence of phonic tics and family history of TS symptoms in our patients, argues in favor of a cause and effect relationship, and the observed association provides evidence for an anatomic substrate for TS and related symptoms.

Adult↗
PubMed2002

Olanzapine treatment for dopaminergic-induced hallucinations.

Atypical antipsychotic medications with lower affinities for D2 receptors are considered useful alternatives to treat drug-induced hallucinations in Parkinson's disease (PD). We conducted a double-blind, placebo-controlled, unforced titration, parallel design study (2:1 drug to placebo randomization ratio) using olanzapine (2.5-10 mg/day to effect) in 30 PD patients with drug-induced hallucinations. We performed an extensive battery of neuropsychological tests, the Unified Parkinson's Disease Rating Scale (UPDRS), assessments of on and off time at baseline and at 9 weeks after starting the medication. Sixteen patients on olanzapine (mean dose, 4.6 mg/night) and 11 on placebo completed the study. Compared with placebo, performance on the UPDRS item 2 (thought disorder), and a structured interview for hallucinations, both tended to improve on drug but neither reached statistical significance. A neuropsychological test battery did not show any significant differences. Total on UPDRS motor scores (P < 0.05) and timed tapping (P < 0.01) worsened while on drug compared to placebo. Bradykinesia (P < 0.01) and gait (P < 0.001) items on the UPDRS largely accounted for this deterioration. After completion of the study, 8 of 16 patients randomly assigned to drug continued olanzapine at a mean dose of 2.4 mg/day. However, at the last recorded visit only 5 of 24 (20.8%) of all patients exposed to drug (including those originally randomly assigned to placebo) remained on olanzapine. In patients with PD, low-dose olanzapine did not significantly improve hallucinations but did worsen motor function.

Aged↗
PubMed2002

Dystonia in spinocerebellar ataxia type 6.

Spinocerebellar ataxias are heterogeneous disorders with overlapping clinical features. Spinocerebellar ataxia-6 is a dominantly inherited condition characterized by relatively pure ataxia with a paucity of other manifestations including extrapyramidal findings. We report on two patients with genetically proven SCA-6 who had dystonia. One patient presented initially with dystonia, which remained the most disabling problem. Dystonia may occur in SCA-6 and can be disabling.

Cerebellum↗
PubMed2002

H-reflex recovery curves differentiate essential tremor, Parkinson's disease, and the combination of essential tremor and Parkinson's disease.

The purpose of this study was to examine H-reflex parameters among the pathophysiologic conditions of essential tremor (ET), Parkinson's disease (PD), combined essential tremor with Parkinson's disease (ETPD), and a control group. H-reflex latencies, amplitude of maximum H-reflex to maximum M-response ratio (H:M), vibration H-reflex to control H-reflex (Hv:Hc), and H-reflex recovery curves (HRRCs) were recorded and compared between a control group and patient groups with ET, early-stage PD, and with ETPD. No statistically or clinically significant differences were found between the patient groups and the control group for latency, H:M ratio, or Hv:Hc ratio. Significantly greater ratio values were observed for the PD group over the other groups for the HRRC tests at each interstimulus interval between 200 and 300 msec (p < 0.05), but values were not different between PD and ETPD patients for intervals between 350 and 1,000 msec. Patients with ET, PD, and ETPD apparently have different underlying pathologies. HRRC tests do not distinguish ET patients from normal, but differentiates specifically between PD and ETPD, and normal individuals. HRRC testing may be a useful method for evaluating pathologies between ET, PD, and ETPD patients.

Adult↗
PubMed2002

Head injury and posttraumatic movement disorders.

WE REVIEW THE phenomenology, pathophysiology, pathological anatomy, and therapy of posttraumatic movement disorders with special emphasis on neurosurgical treatment options. We also explore possible links between craniocerebral trauma and parkinsonism. The cause-effect relationship between head injury and subsequent movement disorder is not fully appreciated. This may be related partially to the delayed appearance of the movement disorder. Movement disorders after severe head injury have been reported in 13 to 66% of patients. Although movement disorders after mild or moderate head injury are frequently transient and, in general, do not result in additional disability, kinetic tremors and dystonia may be a source of marked disability in survivors of severe head injury. Functional stereotactic surgery provides long-term symptomatic and functional benefits in the majority of patients. Thalamic radiofrequency lesioning, although beneficial in some patients, frequently is associated with side effects such as increased dysarthria or gait disturbance, particularly in patients with kinetic tremor secondary to diffuse axonal injury. Deep brain stimulation is used increasingly as an option in such patients. It remains unclear whether pallidal or thalamic targets are more beneficial for treatment of posttraumatic dystonia. Trauma to the central nervous system is an important causative factor in a variety of movement disorders. The mediation of the effects of trauma and the pathophysiology of the development of posttraumatic movement disorders require further study. Functional stereotactic surgery should be considered in patients with disabling movement disorders refractory to medical treatment.

Craniocerebral Trauma↗
PubMed2002

Treatment options for Parkinson's disease.

PURPOSE OF REVIEW: Parkinson's disease is a common neurodegenerative disorder. Clinical trials designed to assess the safety and efficacy of novel neuroprotective as well as symptomatic medical and surgical strategies are being performed to increase and enhance treatment options. The purpose of this review is to summarize these therapeutic options, emphasizing reports published in the last year. RECENT FINDINGS: Experimental therapeutics in Parkinson's disease has focused on prevention of levodopa complications, treatment of dyskinesias associated with levodopa therapy, surgical intervention and neuroprotection. SUMMARY: There are at least four important implications of the recent therapeutic trials: (1) the incidence of levodopa-related dyskinesias decreases as a result of initial use of dopamine agonists; (2) surgery, primarily in the form of the bilateral, high-frequency stimulation of the subthalamic nucleus, is highly effective in patients who are responsive to levodopa but experience marked motor fluctuation or other complications; (3) while neuroprotection has not yet been demonstrated with any currently used therapeutic agent, improved understanding of mechanisms of cell death will undoubtedly result in the discovery of new drugs with potential disease-modifying effects; and (4) implantation of fetal mesencephalon tissue and other grafts may be effective in younger patients with Parkinson's disease, but is associated with significant complications and remains experimental.

Antiparkinson Agents↗
PubMed2002

Secondary causes of paroxysmal dyskinesia.

PxD are sudden, episodic, involuntary movement disorders that may include any combination of dystonia, chorea, athetosis, or ballism. The majority of reported cases are familial or idiopathic; however, there have been several reports of secondary PxD. We report 20 new cases of secondary, non-psychogenic PxD, and review 130 cases reported in the literature. The results suggest that although PxD is a rare disorder, secondary forms may be more common than previously recognized, accounting for 26% of all cases in our series. Secondary cases are notable for their variability in age of onset, the presence of both kinesigenic and non-kinesigenic symptoms in some patients, the prevalence of sensory precipitants, and most importantly, the reversal of symptoms when the underlying etiology is treated in some patients. In addition to MS, other causes to be considered in patients presenting with PxD include cerebral vascular insufficiency and stroke, trauma, metabolic abnormalities, and CNS infections. Awareness of the association of these etiologies with secondary PxD will permit prompt diagnoses and appropriate interventions. Potential pathophysiologic mechanisms including loss of inhibition or primary neuronal hyperactivity are discussed. In addition, recent hypotheses regarding channelopathies in relation to PxD are presented.

Aged↗
PubMedDate not supplied

A peptide-based immunoassay for antibodies against botulinum neurotoxin A.

Cervical dystonia (CD) is due to neck-muscle spasms that cause pain and involuntary contractions resulting in abnormal neck movements and posture. Symptoms can be relieved by injecting the affected muscle with a botulinum neurotoxin (BoNT, usually type A or type B). The therapeutic benefits are impermanent and toxin injections need to be repeated every 3-6 months. In a very small percentage of patients (less with BoNT/A than with BoNT/B) the treatment elicits blocking anti-toxin antibodies (Abs), which reduce or terminate the patient's responsiveness to further treatment. We have recently mapped (Dolimbek et al., 2006) the CD sera Ab-binding profile using a panel of 60, 19-residue peptides that encompassed the entire H chain sequence 449-1296 and overlapped consecutively by 5 residues. Abs in CD sera bound to one or more of the peptides N25, C10, C15, C20, and C31. This suggested the possibility that binding to these peptides could be used for assay of Abs in CD sera. Data analysis reported here found that Ab binding to these regions showed very significant deviations from the control responses. Of these four peptides, C10 showed the most significant level of separation between patient and control groups (p = 5 x 10(-7)) and the theoretical resolution (i.e., ability to distinguish CD patients from control, see full definition under 'Statistical analysis' in Methods), 84%, was about 4% higher than the least resolved response, C31 (p = 6 x 10(-6), resolution 80%). Since the amounts of Abs bound to a given peptide varied with the patient and not all the patients necessarily recognized all four peptides, there was the possibility that binding to combinations of two or more peptides might give a better discriminatory capability. Using two peptides, C10 plus C31, the resolution improved to 87% (p = 4 x 10(-8)). These two peptides appeared to compliment each other and negate the lower resolution of C31. Combination of three peptides gave resolutions that ranged from 85 (N25 + C15 + C31; p = 2 x 10(-7)) to 88% (C10 + C15 + C31; p = 1 x 10(-8)). Finally, using the data of all four peptides, N25 + C10 + C15 + C31, gave a resolution of 86% (p = 1 x 10(-7)). Although these levels of resolution are somewhat lower than that obtained with whole BoNT/A (resolution 97%; p = 6 x 10(-12)), it may be concluded that the two-peptide combination C10 + C31, or the three-peptide combination C10 + C15 + C31 (affording resolutions of 87 and 88%, respectively) provide a good diagnostic, toxin-free procedure for assay of total specific anti-toxin Abs in BoNT/A-treated CD patients.

Amino Acid Sequence↗
PubMedDate not supplied

Cross reaction of tetanus and botulinum neurotoxins A and B and the boosting effect of botulinum neurotoxins A and B on a primary anti-tetanus antibody response.

The present studies were carried out in order to investigate the cross-reaction of botulinum neurotoxins (BoNTs) with human and mouse antibodies against tetanus neurotoxin (TeNT) and determine whether injection of BoNT into a host that has been primed with TeNT would result in boosting of the response to the injected BoNT. Human antisera against TeNT obtained from 9 individuals were found to exhibit substantial cross-reaction with BoNTs A and B. We prepared antibodies (Abs) against inactivated tetanus neurotoxin (TeNT) in outbred mice and determined the binding of these Abs to active TeNT and active botulinum neurotoxins (BoNTs) A and B. Blood samples were collected before immunization (day 0) and on days 42, 82 and 125 after the first injection. The reactions of these sera with the immunizing antigen (inactivated TeNT), active TeNT, active BoNT/A and active BoNT/B were determined. At a fixed dilution (1:62.5 v/v), the sera contained high levels of Abs that reacted with TeNT and also with BoNTs A and B. Throughout the test period (up through day 125) and at different dilutions the cross-reactions of the antisera with BoNT/B were almost twice those with BoNT/A. The reactions of the antisera with the immunizing antigen (inactive TeNT) or with active TeNT were essentially equal throughout the dilution range tested (1:16-1:500 v/v). To determine whether injection of BoNT/A or B into a host that had been primed with TeNT resulted in boosting of the response to the priming antigen (TeNT) as well as BoNT/A or B, mice were primed with TeNT and boosted 21 days later with TeNT, BoNT/A or BoNT/B. Appropriate controls were also employed. Blood samples were collected prior to TeNT priming (day -1) and on days 21, 32, 46 and 67 after priming. In TeNT-primed mice, BoNTs A or B boosted the anti-TeNT Ab responses slightly but had no significant boosting effect on the Ab populations that bind to BoNTs A or B. It is concluded that while Abs against TeNT cross react with BoNTs and the cross reaction with BoNT/B is almost double that of BoNT/A, injection of BoNTs A or B in the presence of a prior active immunity against TeNT is not very likely to make the host mount an Ab response against the injected BoNT.

Animals↗
PubMedDate not supplied

Tetrabenazine treatment for Huntington's disease-associated chorea.

Tetrabenazine (TBZ), a monoamine depleter and dopamine receptor blocker, is used to treat a variety of hyperkinetic movement disorders. The objective was to study the efficacy and tolerability of TBZ for chorea associated with Huntington's disease (HD). Nineteen patients (12 female), mean age 56.3 +/- 12.4 years (range 37-76 years) diagnosed with HD were prospectively evaluated at initial and follow-up visits using a modified Abnormal Involuntary Movement Scale (AIMS). Patients were videotaped, and the randomized videotapes were rated with the motor subset of the AIMS by two investigators who were blinded to treatment assignment. Eighteen patients completed and were rated after 5.9 +/- 3.3 months (range 2-11) at a final mean TBZ dose of 62.5 +/- 37.4 mg/day (range 25-150). The blinded videotaped motor scores showed that 15 were better on TBZ, 2 were better before TBZ, and 1 was unchanged (p < 0.001, Wilcoxon signed rank test). The mean score improved from 16.2 +/- 4.8 to 12.8 +/- 4.4. Adverse events included akathisia, insomnia, constipation, depression, drooling, and subjective weakness. All 18 of these patients have continued to take TBZ since completion of the study. TBZ was well tolerated and resulted in a significant improvement in modified AIMS scores in HD patients. These results support the use of TBZ for chorea in patients with HD.

Adrenergic Uptake Inhibitors↗
PubMedDate not supplied

Dopaminergic properties and experimental anti-parkinsonian effects of IPX750 in rodent models of Parkinson disease.

With a view toward improving the neural bioavailability of administered dopaminergic compounds, including dopamine, synthetic efforts have been directed toward enhancing the brain bioavailability of these compounds by accessing cellular sugar transport systems with stereoselective dopaminergic drugs. While synthesis and chemistry of the resultant class of compounds has recently been described in US Patent No. 6,548,484, the associated biologic properties have not previously been reported. One member of this new class, IPX-750, is a pro-drug dopamine-gluconamine designed to retain stereospecificity of binding at: glucose transporters (GLUT 1/GLUT 3 and intestinal Na/glucose co-transporters SGLT1), dopamine transporter (DAT); and, dopaminergic receptors of the D1/D2 families. Designed to be cleavable by tissue amidases, results reported here show that intact IPX-750 pro-drug retains dopaminergic agonist binding and biologic activities both in vitro and in vivo. IPX-750, like dopamine, exhibited predominant D5/D1 binding specificity with lower binding activity at D2. As expected, binding was highly stereo-specific, ie, IPX-760, a benzamide differing in just a hydrogen atom and keto oxygen from IPX-750, bound with 6-fold lower activity at D5. In cell culture, activation resulted from binding of IPX-750 at D1 or D5 in transfected cells was measured by increased intracellular cAMP. Interestingly, considering prior reported in vitro toxicity of dopamine oxidized and metabolic product dopamine, no evidence of in vitro toxicity was observed at up to 72 hrs in cell cultures at the EC50 of IPX-750 for increasing intracellular cAMP. IPX-750 was evaluated in the Parkinson's disease animal models, including MPTP mouse model, the 6-hydroxydopamine (6-OHDA) rat model and the Nurr1(+/-) knockout mouse model. In MPTP-lesioned and Nurr1+/- knockout mice, IPX-750 significantly increased Rota-rod time. In 6-OHDA-lesioned rats, IPX-750 significantly decreased apomorphine (APO)-induced rotation. Worthy of note, after cessation of IPX-750 treatments the anti-parkinsonian activity in MPTP-lesioned and Nurr1+/- mice required about 2 weeks to washout, suggesting a possible biologic reservoir of drug. In addition, after eight weeks of twice daily administration of 20 mg/kg IPX-750, mice did not show statistical difference in the total number of TH-positive neurons in substantia nigra (SN). These combined results suggest (i) that stereo-specific glycoconjugation may be an effective method to improve penetrability of drugs through the blood brain barrier; (ii) treatment with bioavailable IPX-750 in vitro did not show evidence for neurotoxicity; and, (iii) IPX-750 possesses dopaminergic properties and exerts anti-parkinsonian effects in three different PD rodent models, suggesting therapeutic potential for this new class of drugs in treating dopamine deficiency diseases.

Animals↗
PubMedDate not supplied

An open-label pilot study of levetiracetam for essential tremor.

The objective of this study was to determine whether levetiracetam warrants further investigation as a treatment of essential tremor (ET). The authors conducted a 4 -week, open label trial of levetiracetam (Keppra, UCB Pharmaceuticals) in 10 patients diagnosed with ET. Patients were assessed with the complete Tremor Rating Scale (TRS), global impression measures, and adverse events at baseline, after 2 weeks low-dose 500 mg bid and at 4 weeks high-dose 1500 mg bid. All 10 subjects (mean age, 68.6 +/- 7.4 years; seven men, 9 with a positive family history of ET) completed the trial. The TRS observed tremor section modestly improved in 8 subjects (P <0.01). The TRS writing section, water pouring section, and activities of daily living section did not change, and visual analog scores did not change. Subjects rated themselves as "much improved" (n=3), moderately improved (n=1), unchanged (n=1), and mildly worse (n=5). Adverse events included dizziness (n=2), sedation (n=1), and nervousness (n=1). Levetiracetam was well tolerated but failed to improve tremor consistently in this small trial.

Aged↗
PubMedDate not supplied

Evidence-based review of patient-reported outcomes with botulinum toxin type A.

This review systematically examines the effects of botulinum toxin type A (BTX-A) on patient-reported outcomes across disorders using evidence-based criteria. The evidence provided by these studies ranged from randomized, controlled trials to case series. The effects of BTX-A on quality of life or global treatment outcomes were assessed in 48 studies across 16 different conditions. All but 7 of these reported benefits of BTX-A over baseline or the comparator condition (placebo or other treatment). The effects of BTX-A on impairment, activities, or participation were assessed in 46 studies across 17 different conditions. All but 4 reported benefits of BTX-A over baseline or the comparison group. The effects of BTX-A on satisfaction or preference were assessed in 14 studies across 11 different conditions, all of which reported high rates of satisfaction with BTX-A or preference over the comparator. These studies provide evidence that BTX-A exerts meaningful benefits on the quality of life of patients treated with this biologic agent.

Anti-Dyskinesia Agents↗
PubMedDate not supplied

Is history of depression a contraindication to treatment with tetrabenazine?

OBJECTIVE: To determine whether a history of depression predisposes hyperkinetic patients treated with tetrabenazine (TBZ) to a recurrence or worsening of this symptom. METHODS: We retrospectively reviewed the charts of 518 patients treated with TBZ to determine the frequency of depression and other adverse events. Charts were screened for the preexistence, development, or exacerbation of depression during the course of treatment. RESULTS: The most common adverse events related to TBZ were somnolence (27.4%), depression (15.1%), parkinsonism (11.8%), and akathisia (8.9%); 78 patients (15.1%) experienced depression for the first time or an exacerbation of existing depression. Of those patients with no history of depression, 28 (11.4%) of 246 were newly diagnosed with depression. Patients with a documented history of depression experienced a significantly higher rate of worsening in 50 (18.4%) of 272 cases (P = 0.03). However, patients with a history of depression experienced more improvement of their hyperkinesia compared to those without a history of depression (P < 0.01). CONCLUSIONS: Depression, an adverse event of TBZ, is more likely to occur or worsen in patients with a preexisting history of depression.

Adolescent↗