Parkinson Disease: Giladi N

Goetz CG, Poewe W, Rascol O, Sampaio C, Stebbins GT, Counsell C, Giladi N, Holloway RG, Moore CG, Wenning GK, Yahr MD, Seidl L, Anonymous00253. · Rush University Medical Center, 1725 W. Harrison Street, Chicago, IL 60612, USA. · Mov Disord. · Pubmed #15372591 links to  free full text

Abstract: The Movement Disorder Society Task Force for Rating Scales for Parkinson's disease (PD) prepared a critique of the Hoehn and Yahr scale (HY). Strengths of the HY scale include its wide utilization and acceptance. Progressively higher stages correlate with neuroimaging studies of dopaminergic loss, and high correlations exist between the HY scale and some standardized scales of motor impairment, disability, and quality of life. Weaknesses include the scale's mixing of impairment and disability and its non-linearity. Because the HY scale is weighted heavily toward postural instability as the primary index of disease severity, it does not capture completely impairments or disability from other motor features of PD and gives no information on nonmotor problems. Direct clinimetric testing of the HY scale has been very limited, but the scale fulfills at least some criteria for reliability and validity, especially for the midranges of the scale (Stages 2-4). Although a "modified HY scale" that includes 0.5 increments has been adopted widely, no clinimetric data are available on this adaptation. The Task Force recommends that: (1) the HY scale be used in its original form for demographic presentation of patient groups; (2) when the HY scale is used for group description, medians and ranges should be reported and analysis of changes should use nonparametric methods; (3) in research settings, the HY scale is useful primarily for defining inclusion/exclusion criteria; (4) to retain simplicity, clinicians should "rate what you see" and therefore incorporate comorbidities when assigning a HY stage; and (5) because of the wide usage of the modified HY scale with 0.5 increments, this adaptation warrants clinimetric testing. Without such testing, however, the original five-point scales should be maintained.

Giladi N, Nieuwboer A. · No affiliation provided · Mov Disord. · Pubmed #18668629 No free full text.

This publication has no abstract.

Herman T, Giladi N, Hausdorff JM. · Laboratory for Gait and Neurodynamics, Movement Disorders Unit and Parkinson Center, Department of Neurology, Tel-Aviv Sourasky Medical Center, 6 Weizman Street, 64239, Tel Aviv, Israel. · J Neural Transm. · Pubmed #18982238 No free full text.

Abstract: This report reviews recent investigations of the effects of treadmill training (TT) on the gait of patients with Parkinson's disease. A literature search identified 14 relevant studies. Three studies reported on the immediate effects of TT; over-ground walking improved (e.g., increased speed and stride length) after one treadmill session. Effects persisted even 15 min later. Eleven longer-term trials demonstrated feasibility, safety and efficacy, reporting positive benefits in gait speed, stride length and other measures such as disease severity (e.g., Unified Parkinson's Disease Rating Scale) and health-related quality of life, even several weeks after cessation of the TT. Long-term carryover effects also raise the possibility that TT may elicit positive neural plastic changes. While encouraging, the work to date is preliminary; none of the identified studies received a quality rating of Gold or level Ia. Additional high quality randomized controlled studies are needed before TT can be recommended with evidence-based support.

Giladi N. · Movement Disorders Unit, Department of Neurology, Tel-Aviv Sourasky Medical Center, Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel. · Mov Disord. · Pubmed #18668620 No free full text.

Abstract: Freezing of gait (FOG) is frequently considered as one of the dopamine-resistant motor symptoms of Parkinsonism. Recent studies have clearly demonstrated that the Off-related FOG is improved by levodopa (L-dopa) or entacapone treatment. L-dopa can decrease duration of each FOG episode as well as its frequency. On-related FOGs are not common and difficult to diagnose. Only in the most advanced stages of the disease, FOGs are resistant to treatment as many other symptoms. Off-related FOGs are likely to be improved by dopamine agonists (DAs), but this has never been looked at systematically. In contrast, DA treatment might provoke FOG, and in two pivotal studies when DAs were compared to L-dopa in early stages of Parkinson's disease, the DA-treated arms experienced more FOGs. MAO-B inhibitors (selegiline and rasagiline) can decrease FOG frequency or severity, but its clinical significance is still unknown. L-Threo-DOPS has been reported to have a symptomatic beneficial effect in patients with pure freezing syndrome, but small-scale, controlled trials in Parkinson's disease could not support those early observations. Botulinum toxin injected into the calf muscles has been suggested to have a symptomatic benefit. However, double-blind, prospective studies could not support that early observation and increased fall risk in the injected patients has put this direction of treatment on hold. The potential benefit of amantadine, antidepressive drugs, acetylcholine esterase inhibitors, and methylphenidate on FOG has been studied in small-scale studies, and there is a need for prospective studies to understand the future role of those drugs.

Rosner S, Giladi N, Orr-Urtreger A. · The Genetic Institute, Tel-Aviv Sourasky Medical Center, Tel-Aviv University, Tel-Aviv, Israel. · Acta Pharmacol Sin. · Pubmed #18158863 links to  free full text

Abstract: Parkinson's disease (PD) is a neurodegenerative disorder affecting a significant proportion of the ageing population. The etiology is unknown and it is likely due to a multifactorial interaction of genes and the environment on the background of ageing. Findings in the last decade suggest that the contribution of genetics to familial forms of PD is much greater than previously appreciated. Twelve loci are now associated with highly penetrant autosomal dominant or recessive PD, and causative mutations have been identified in eight genes with mutation carriers often characterized by a phenotype indistinguishable from idiopathic disease. To date, PD pharmacotherapy is symptomatic only and does not slow disease progression. Understanding how genetic mutations cause familial PD is likely to clarify molecular mechanisms underlying PD in general and will provide a guide for the development of novel therapies, both preventative and palliative, applicable to all forms of parkinsonism. This review outlines the advances in the study of the genetic background of PD and their possible clinical implications.

Merims D, Giladi N. · Movement Disorders Unit, Department of Neurology, Tel-Aviv Sourasky Medical Center, Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel. · Parkinsonism Relat Disord. · Pubmed #17988927 No free full text.

Abstract: Degeneration of the dopaminergic system in Parkinson's disease and longstanding exposure to dopaminergic drugs may cause reward system malfunction. This may manifest as addiction to l-dopa and behavioral disturbances associated with the impulse control system. These disturbances include: gambling, excessive spending (shopping), hypersexuality and binge eating. We included one such patient's personal story to emphasize the devastating consequences of these potentially reversible phenomena: the patient describes in his own words how gambling induced by an exposure dopamine agonist therapy significantly worsened his disease-related difficulties.

Giladi N, Balash Y. · Movement Disorders Unit, Department of Neurology, Tel-Aviv Sourasky Medical Center, Tel-Aviv, Israel. · J Neural Transm Suppl. · Pubmed #17017548 No free full text.

Abstract: Gait is affected in all stages of Parkinson's disease (PD) and is one of the hallmarks for disease progression. The fear of getting into the wheel chair is one of the first thoughts many patients ask about when the diagnosis of PD is given. At the early stages of the disease gait disturbances are present and can be measured but in most patients it does not cause significant functional disturbances. In contrast, as the disease progress, gait disturbances and postural control abnormalities are becoming major causes for lost of mobility and falls. These unfortunate consequences should be forecasted at the early stages of the disease and a preventive approach should be taken. Treatment of gait disturbances at the early stages of the disease is mainly to encourage patients to exercise and walk daily and by drugs in those with disabling symptoms. At the advanced stages, treatment should be aggressive in order to keep the patient walking safely. Drugs, physiotherapy and functional neurosurgery should be used wisely for best outcomes and least side effects. When time comes and the risk of falls is very significant, walking aids should be suggested and if no other option is left, wheel chair is a very reasonable option to maintain mobility out of home, preserving quality of life and avoiding falls with all it severe consequences.

Giladi N, Hausdorff JM. · Movement Disorders Unit, NPF Center for Parkinson's Disease, Department of Neurology, Tel-Aviv Sourasky Medical Center, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel. · J Neurol Sci. · Pubmed #16780886 No free full text.

Abstract: Freezing of gait (FOG) is a disabling episodic gait disturbance that is common among patients with Parkinsonism. FOG typically lasts a few seconds and is associated with a unique sensation: the patient feels that his feet are glued to the ground, causing him to remain in place despite making a concerted effort to overcome the motor block and move forward. Traditionally, FOG has been viewed as a motor symptom of advanced Parkinson's disease. Here we describe evidence which demonstrates that mental conditions also likely play an important role in the pathogenesis of FOG. Stress, anxiety, depression and cognitively challenging situations are associated with FOG, and may set the stage for and increase the likelihood that FOG occurs. A conceptual model that explains how mental conditions may modulate FOG is developed.

Bloem BR, Hausdorff JM, Visser JE, Giladi N. · Department of Neurology, University Medical Centre St. Radboud, Nijmegen, The Netherlands. · Mov Disord. · Pubmed #15300651 No free full text.

Abstract: Falls and freezing of gait are two "episodic" phenomena that are common in Parkinson's disease. Both symptoms are often incapacitating for affected patients, as the associated physical and psychosocial consequences have a great impact on the patients' quality of life, and survival is diminished. Furthermore, the resultant loss of independence and the treatment costs of injuries add substantially to the health care expenditures associated with Parkinson's disease. In this clinically oriented review, we summarise recent insights into falls and freezing of gait and highlight their similarities, differences, and links. Topics covered include the clinical presentation, recent ideas about the underlying pathophysiology, and the possibilities for treatment. A review of the literature and the current state-of-the-art suggests that clinicians should not feel deterred by the complex nature of falls and freezing of gait; a careful clinical approach may lead to an individually tailored treatment, which can offer at least partial relief for many affected patients.

Rubinstein TC, Giladi N, Hausdorff JM. · Movement Disorders Unit, Neurology Department, Tel-Aviv Sourasky Medical Center, and Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel. · Mov Disord. · Pubmed #12465051 No free full text.

Abstract: Gait disturbances are among the primary symptoms of Parkinson's disease (PD) and contribute significantly to a patient's loss of function and independence. Standard treatment includes antiparkinsonian drugs, primarily levodopa. In addition to the standard drug regime, physical therapy is often prescribed to help manage the disease. In recent years, there have been promising reports of physical therapy programs combined with various types of sensory cueing for PD. In this brief review of the literature, we summarize the evidence regarding the clinical efficacy of different physical therapy programs for PD, specifically with respect to improving gait. We also discuss the potential therapeutic mechanisms of sensory cueing and review the studies that have used cueing in the treatment of gait in PD. This review of the literature shows two key findings: (1) despite its relatively long history, the evidence supporting the efficacy of conventional physical therapy for treatment of gait in PD is not strong; and (2) although further investigation is needed, sensory cueing appears to be a powerful means of improving gait in PD.

Aziz TZ, Nandi D, Parkin S, Liu X, Giladi N, Bain P, Gregory RG, Joint C, Scott RB, Stein JF. · University Laboratory of Physiology, Department of Neurosurgery, Radcliffe Infirmary, Oxford, UK. · Stereotact Funct Neurosurg. · Pubmed #12378062 No free full text.

Abstract: The small size and surrounding neuronal structures and fibre tracts make the STN a difficult stereotactic target. In this article we present the technique used by us to target the STN. Our combined experience from two centres comprises 18 lesions and 27 stimulator implants in the STN. Our criteria for patient selection and the use of MRI, frame-on CT and volumetric image fusion are presented. The role of a movement disorder specialist neurologist in the operating theatre, local field potential recording, impedance monitoring, macrostimulation, post-operative CT/MRI and test stimulation are detailed.

Giladi N, Balash J. · Movement Disorders Unit, Department of Neurology, Tel-Aviv Sourasky Medical Center, Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel. · Neurol Neurochir Pol. · Pubmed #12001655 No free full text.

This publication has no abstract.

Giladi N. · Movement Disorders Unit, Tel-Aviv Medical Center, Tel-Aviv University, Tel-Aviv 64239, Israel. · Adv Neurol. · Pubmed #11553986 No free full text.

This publication has no abstract.

Giladi N. · Movement Disorders Unit, Department of Neurology, Tel Aviv Medical Center, Tel Aviv University, Tel Aviv, Israel 64239. · Adv Neurol. · Pubmed #11347222 No free full text.

This publication has no abstract.

Giladi N, Melamed E. · Department of Neurology, Tel Aviv Sourasky Medical Center, Rabin Medical Center (Beilinson Campus), Petah Tiqva, Israel. · Isr Med Assoc J. · Pubmed #10897238 links to  free full text

This publication has no abstract.

Korczyn AD, Giladi N. · Department of Neurology, Tel-Aviv Medical Center, Ramat-Aviv, Israel. · Adv Neurol. · Pubmed #10410753 No free full text.

This publication has no abstract.

Kandinov B, Giladi N, Korczyn AD. · Department of Physiology and Pharmacology, Tel Aviv University, Tel Aviv, Israel. · Parkinsonism Relat Disord. · Pubmed #18434232 No free full text.

Abstract: Cigarette smoking, coffee and tea drinking may protect against Parkinson's disease (PD). These factors were assessed, retrospectively, to measure their effect on the age of PD onset. The study population consisted of 278 consecutive PD patients. Smoking > or =10 pack-years delayed age of PD onset by 3.2 years (p<0.05). Consumption of tea more than 3 cups per day delayed age of motor symptoms onset by 7.7 years (p<0.01). Coffee consumption exceeding 3 cups per day advanced the age of PD onset by 4.8 years (p=0.03). Thus, tea consumption and smoking can delay the age of PD onset, while coffee drinking may have the opposite effect.

Hausdorff JM, Lowenthal J, Herman T, Gruendlinger L, Peretz C, Giladi N. · Laboratory for Gait and Neurodynamics, Movement Disorders Unit and Parkinson Center, Department of Neurology, Tel Aviv Sourasky Medical Center, 6 Weizman Street, Tel Aviv 64239, Israel. · Eur J Neurosci. · Pubmed #17953624 No free full text.

Abstract: Patients with Parkinson's disease (PD) walk with a shortened stride length and high stride-to-stride variability, a measure associated with fall risk. Rhythmic auditory stimulation (RAS) improves stride length but the effects on stride-to-stride variability, a marker of fall risk, are unknown. The effects of RAS on stride time variability, swing time variability and spatial-temporal measures were examined during 100-m walks with the RAS beat set to 100 and 110% of each subject's usual cadence in 29 patients with idiopathic PD and 26 healthy age-matched controls. Carryover effects were also evaluated. During usual walking, variability was significantly higher (worse) in the patients with PD compared with the controls (P < 0.01). For the patients with PD, RAS at 100% improved gait speed, stride length and swing time (P < 0.02) but did not significantly affect variability. With RAS at 110%, reductions in variability were also observed (P < 0.03) and these effects persisted 2 and 15 min later. In the control subjects, the positive effects of RAS were not observed. For example, RAS increased stride time variability at 100 and 110%. These results demonstrate that RAS enables more automatic movement and reduces stride-to-stride variability in patients with PD. Further, these improvements are not simply a by-product of changes in speed or stride length. After walking with RAS, there also appears to be a carryover effect that supports the possibility of motor plasticity in the networks controlling rhythmicity in PD and the potential for using RAS as an intervention to improve mobility and reduce fall risk.

Plotnik M, Giladi N, Balash Y, Peretz C, Hausdorff JM. · Movement Disorders Unit, Department of Neurology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel. · Ann Neurol. · Pubmed #15852404 No free full text.

Abstract: Freezing of gait (FOG) is a disabling phenomenon common in patients with advanced Parkinson's disease (PD). The cause of FOG is unclear. The objective of this study was to explore a novel hypothesis stating that FOG is related to asymmetric motor performance. We compared PD patients that experience FOG episodes (PD+FOG) with PD patients that do not (PD-FOG) and studied the relationship of FOG to asymmetry in gait and in rhythmic hand movement performance to determine whether potential FOG-related gait asymmetry is unique to walking or whether it is systemic. Subjects were tested in an "off" (unmedicated) and again in an "on" (medicated) state. Gait was more asymmetric in PD+FOG than in PD-FOG during "off" state (p = 0.005) and during "on" (p = 0.016). Rhythmicity of foot swing in one leg was correlated with the other leg in PD-FOG but not in PD+FOG. There was no difference in asymmetry in performance of rhythmic hand movements between the two groups. No correlation was found between asymmetry of clinical symptoms and gait asymmetry. Taken together, the results of this study suggest that bilateral uncoordinated gait and marked gait asymmetry, but not asymmetry in motor performance in general, are associated with FOG.

Djaldetti R, Giladi N, Hassin-Baer S, Shabtai H, Melamed E. · Department of Neurology, Rabin Medical Center, Beilinson Campus, Petah Tiqva 49100, Israel. · Clin Neuropharmacol. · Pubmed #14646613 No free full text.

Abstract: "Dose failures" and "delayed on" phenomena following an intake of levodopa dose in patients with Parkinson's disease (PD) with motor fluctuations may be caused by stagnation of poorly soluble levodopa in the atonic stomach. Etilevodopa is a unique, highly soluble prodrug of levodopa. When ingested, etilevodopa is more readily dissolved in the stomach than levodopa. It passes unchanged through the stomach to the duodenum, where it is rapidly hydrolyzed by local esterases and rapidly absorbed as levodopa. To compare the pharmacokinetics of three different modes of etilevodopa/carbidopa administration with standard levodopa/carbidopa tablets in fluctuating PD patients, 29 patients with PD and response fluctuations were enrolled in an open-label, randomized, four-way crossover study of single doses of 4 treatments: swallowed etilevodopa/carbidopa tablets, etilevodopa/carbidopa tablets dissolved in water, etilevodopa oral solution with carbidopa tablets, and standard levodopa/carbidopa tablets. To measure the maximal concentration (Cmax), time to Cmax (tmax), and area under the curve (AUC) of plasma levodopa, etilevodopa, and carbidopa, blood samples were drawn before drug administration and at intervals up to 240 minutes thereafter. Plasma levodopa tmax was significantly shorter with all three modes of administration of etilevodopa (mean of about 30 minutes) than with levodopa treatment (mean of 54 minutes). During the first 45 minutes after drug ingestion, plasma levodopa AUC was significantly greater after etilevodopa administration than after levodopa administration. Levodopa AUC for 0 to 1 hour and 0 to 2 hours were also significantly greater following administration of etilevodopa/carbidopa swallowed tablets than following administration of levodopa/carbidopa tablets. Mean levodopa Cmax was in the range 2.3 to 2.7 microg/mL for all treatments. Levodopa Cmax was significantly greater following treatment with etilevodopa swallowed tablets than with levodopa tablets. Etilevodopa/carbidopa was well tolerated, with a safety profile comparable to that of levodopa/carbidopa. The shorter levodopa tmax observed with etilevodopa potentially translates to a shorter time to "on". Clinical trials with etilevodopa/carbidopa tablets should be carried out in PD patients with response fluctuations such as "delayed on" and "dose failures".

Giladi N, Shabtai H, Gurevich T, Benbunan B, Anca M, Korczyn AD. · Department of Neurology, Tel-Aviv Sourasky Medical Center, Israel. · Acta Neurol Scand. · Pubmed #14616309 No free full text.

Abstract: OBJECTIVES: To study the efficacy of cholinesterase inhibitors in the treatment of dementia in patients with Parkinson's disease (PD). METHODS: We treated twenty-eight demented patients with PD openly for 26 weeks with rivastigmine (mean daily dose 7.2 +/- 3.3 mg/day). Baseline scores were compared with those at weeks 12, 26 and after 8 weeks of washout. RESULTS: Twenty patients completed 26 weeks of treatment and eight dropped out because of side effects. The Unified Parkinson's Disease Rating Scale mental subscore improved significantly at week 26 (P < 0.01) while the motor score (part III) did not change. The mean ADAScog total score improved by 7.3 points at week 26 (P < 0.002). The subscores for recognition, word finding, remembering instructions and concentration items of the ADAScog improved significantly as well (P < 0.02, P < 0.05, P < 0.005 and P < 0.003, respectively). CONCLUSIONS: Rivastigmine may improve the cognitive functions in PD patients with dementia with no worsening of motor function.

Fogelson N, Kogan E, Korczyn AD, Giladi N, Shabtai H, Neufeld MY. · Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel. · Acta Neurol Scand. · Pubmed #12675697 No free full text.

Abstract: OBJECTIVES: Quantitative electroencephalogram (qEEG) can be used to measure the effects of drugs on the brain. We studied the effects of rivastigmine on the qEEG in Parkinson's disease (PD) patients with dementia. SUBJECTS AND METHODS: Demented PD patients (n=19) were treated with rivastigmine in an open label study. Recordings were obtained prior to and following 12 weeks of treatment. Results were analyzed using two-way ANOVA with repeated measures. RESULTS: A significant increase in the relative alpha (P < 0.05) activity was observed after treatment with rivastigmine. This was general rather than localized to specific brain surface areas. An increase in beta activity and decrease in the slower frequencies (delta and theta) were also observed; however, these were not statistically significant. CONCLUSION: qEEG may serve as an objective tool to monitor the effects of antidementia drug therapy. The changes characterized by increased faster frequencies and decreased slower frequencies that were observed may indicate increased arousal or improvement in the cognitive state of the patients as a consequence of the treatment with rivastigmine.

Rabey JM, Sagi I, Huberman M, Melamed E, Korczyn A, Giladi N, Inzelberg R, Djaldetti R, Klein C, Berecz G, Anonymous00201. · Department of Neurology, Assaf Harofeh Medical Center, Zerifin, Sackler Faculty of Medicine, Tel-Aviv University, Israel. · Clin Neuropharmacol. · Pubmed #11575866 No free full text.

Abstract: Rasagiline mesylate (TVP-1012) is a potent, selective, non-reversible MAO-B inhibitor, without the tyramine-potentiating effect and with neuroprotective activities. The benefit of rasagiline as monotherapy in patients with early Parkinson's disease (PD) has already been reported. To evaluate the safety, tolerability, and clinical effect of rasagiline as adjunctive therapy to levodopa, a multicenter, double-blind, randomized, placebo-controlled, parallel-group study (0.5, 1, and 2 mg/d) was conducted for 12 weeks in 70 patients with PD (mean age, 57.4 y; mean disease duration, 5.7 y; 32 patients had motor fluctuations). A beneficial clinical effect was observed in fluctuating patients treated with rasagiline (all doses), expressed as a decrease in total Unified Parkinson's Disease Rating Scale (UPDRS) score (23.0% vs 8.5% in the placebo group). The treatment effect was still evident 6 weeks after drug discontinuation (in all doses). The safety and tolerability of rasagiline were good. Adverse events were no different than those of patients taking placebo. Almost complete platelet MAO-B inhibition was obtained at all rasagiline doses. This study has demonstrated that rasagiline (up to 2 mg/day) has a good safety profile and a beneficial clinical effect in fluctuating patients with PD when given as an add-on to chronic levodopa therapy.

Giladi N, Gurevich T, Shabtai H, Paleacu D, Simon ES. · Department of Neurology, Tel-Aviv Sourasky Medical Center, Israel. · J Neurol. · Pubmed #11517998 No free full text.

Abstract: BACKGROUND: Freezing of gait (FOG) is a common and very disabling parkinsonian symptom, which is poorly understood and responds unsatisfactorily to medical treatment. We recently reported a unique patient with Parkinson's disease (PD) who had significant alleviation of FOG shortly after she was injected with botulinum toxin type A (BTX-A) for foot dystonia (Giladi et al. 1997). OBJECTIVE: To assess the effect of BTX-A injections into the calf muscles of parkinsonian patients on FOG. METHOD: BTX-A was injected in an open fashion into the calf muscles of 10 parkinsonian patients (age 55-75 years) with FOG as a predominant symptom. Response of FOG was assessed subjectively by the patient from worsening (-1) to marked improvement (+3). One patient was injected in a single blind fashion with saline or BTX-A after he had an initial good response. RESULTS: Seven patients reported different rates of improvement of FOG severity in 15 out of 17 therapeutic sessions. Four patients (40%) reported marked improvement (+3) of FOG in 5 sessions. Two patients reported no effect in two sessions. The mean duration of improvement was 6 weeks (range 1-12 weeks) with definite deterioration afterwards. The patient who was injected in a single blind fashion did not respond to saline injections but improved significantly with BTX-A treatment. CONCLUSIONS: We observed a clear temporal relationship between BTX-A injections into the calf muscles of parkinsonian patients and improvement of FOG. A double blind placebo controlled prospective study is needed before any conclusions can be drawn about the role of BTX-A injection in FOG.

Giladi N, McDermott MP, Fahn S, Przedborski S, Jankovic J, Stern M, Tanner C, Anonymous00234. · Movement Disorders Division, Department of Neurology, Columbia-Presbyterian Medical Center, New York, NY, USA. · Neurology. · Pubmed #11425939 No free full text.

Abstract: OBJECTIVE: To study the development of freezing of gait in PD. BACKGROUND: Freezing of gait is a common, disabling, and poorly understood symptom in PD. METHODS: The authors analyzed data from 800 patients with early PD from the Deprenyl and Tocopherol Antioxidative Therapy of Parkinsonism (DATATOP) clinical trial who were assigned either placebo, deprenyl, tocopherol, or the combination of deprenyl and tocopherol. The primary outcome measure was the time from randomization until the freezing of gait score on the Unified Parkinson's Disease Rating Scale (UPDRS) became positive. RESULTS: Fifty-seven patients (7.1%) had freezing of gait at study entry and 193 (26%) of the remaining patients experienced the symptom by the end of the follow-up period. Those with freezing of gait at baseline had significantly more advanced disease than those without the symptom, as measured by total UPDRS and Hoehn and Yahr stage. High baseline risk factors for developing freezing of gait during the follow-up period were the onset of PD with a gait disorder; higher scores of rigidity, postural instability, bradykinesia and speech; and longer disease duration. In contrast, tremor was strongly associated with a decreased risk for freezing of gait. At the end of follow-up, the signs most strongly associated with the freezing phenomenon were gait, balance, and speech disorders, not rigidity or bradykinesia. Deprenyl treatment was strongly associated with a decreased risk for developing freezing of gait; tocopherol had no effect. CONCLUSIONS: Freezing of gait is directly related to duration of PD. Risk factors at onset of disease are the absence of tremor and PD beginning as a gait disorder. The development of freezing of gait in the course of the illness is strongly associated with the development of balance and speech problems, less so with the worsening of bradykinesia, and is not associated with the progression of rigidity. These results support the concept that the freezing phenomenon is distinct from bradykinesia. Deprenyl, in the absence of L-dopa, was found to be an effective prophylactic treatment and should be considered for patients with PD who have an onset of gait difficulty.