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Biomedical subjects

N Giladi

Publications and source records attributed to N Giladi.

At least 19 recordsLinked to original sources
PubMed2003

Impaired regulation of stride variability in Parkinson's disease subjects with freezing of gait.

Patients with Parkinson's disease (PD) often experience freezing of gait, a debilitating phenomenon during which the subject suddenly becomes unable to start walking or to continue to move forward. Little is known about the gait of those subjects with PD who experience freezing of gait or the pathophysiology of freezing. One possibility is that freezing of gait is a truly paroxysmal phenomenon and that the usual walking pattern of subjects who experience freezing of gait is not different than that of other patients with PD who do not experience these transient episodes of freezing of gait. On the other hand, a recent study noted gait changes just prior to freezing and concluded that dyscontrol of the cadence of walking contributes to freezing. To address this question, we compared the gait of PD subjects with freezing of gait to PD subjects without freezing of gait. Given the potential importance of the dyscontrol of the cadence of walking in freezing, we focused on two aspects of gait dynamics: the average stride time (the inverse of cadence, a measure of the walking pace or rate) and the variability of the stride time (a measure of "dyscontrol," arrhythmicity and unsteadiness). We found that although the average stride time was similar in subjects with and without freezing, stride-to-stride variability was markedly increased among PD subjects with freezing of gait compared to those without freezing of gait, both while "on" (P<0.020) and "off" (P<0.002) anti-parkinsonian medications. Further, we found that increased gait variability was not related to other measures of motor control (while off medications) and levodopa apparently reduced gait variability, both in subjects with and without freezing. These results suggest that a paradigm shift should take place in our view of freezing of gait. PD subjects with freezing of gait have a continuous gait disturbance: the ability to regulate the stride-to-stride variations in gait timing and maintain a stable walking rhythm is markedly impaired in subjects with freezing of gait. In addition, these findings suggest that the inability to control cadence might play an important role in this debilitating phenomenon and highlight the key role of dopamine-mediated pathways in the stride-to-stride regulation of walking.

Aged↗
PubMed2003

Relationship between freezing of gait (FOG) and other features of Parkinson's: FOG is not correlated with bradykinesia.

BACKGROUND: The pathophysiology of freezing of gait (FOG) is unclear. OBJECTIVE: To assess the relationships between FOG and other parkinsonian features in Parkinson's disease (PD), focusing on levodopa effects. METHODS: Nineteen PD patients with significant FOG in "off" were assessed while "off" and "on". Three observers independently viewed videotapes of a 130-m walk and scored FOG frequency. The Unified Parkinson's disease Rating Scale was used to evaluate clinical state. RESULTS: FOG frequency was not correlated with other parkinsonian features in "off" and only with speech and writing in "on". Levodopa significantly decreased FOG frequency (p<0.001). This reduction was strongly correlated with improvement of tremor (R=0.80, p<0.01) and speech (R=0.62, p<0.05), but not with improvement in rigidity, bradykinesia, or balance. CONCLUSION: Levodopa decreases FOG in PD. FOG is apparently an independent motor symptom, caused by a paroxysmal pathology that is different from that responsible for bradykinesia, rigidity or postural instability.

Antiparkinson Agents↗
PubMed2003

Effects of rivastigmine on the quantitative EEG in demented Parkinsonian patients.

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.

Aged↗
PubMed2003

Characterization of freezing of gait subtypes and the response of each to levodopa in Parkinson's disease.

To assess the effect of levodopa on distinct freezing of gait (FOG) subtypes in patients with 'off' FOG. Nineteen patients (12 men, mean age 62.0 +/- 8.4 years) with Parkinson's disease and clinically significant FOG during 'off' states were videotaped whilst walking 130 m during 'off' and 'on' states. Three independent observers characterized the type, duration, and clinical manifestations and quantified FOG by analyzing the videotapes. Their combined mean scores were used for statistical analysis. The intra-class correlation coefficient assessed inter-observer reliability. Wilcoxon and Friedman tests evaluated differences in mean frequencies of FOG characteristics. During 'off' states, FOG was elicited by turns (63%), starts (23%), walking through narrow spaces (12%) and reaching destinations (9%). These respective values were only 14, 4, 2 and 1% during 'on' states (P < 0.011). Moving forward with very small steps and leg trembling in place were the most common manifestations of FOG; total akinesia was rare. Most FOG episodes took <10 s and tended to be shorter during 'on' states. Levodopa significantly decreased FOG frequency (P < 0.0001) and the number of episodes with akinesia (P < 0.001). Distinction amongst FOG subtypes enables evaluation of distinctive therapeutic response. Levodopa helps in reducing the frequency and duration of 'off'-related FOG.

Aged↗
PubMed2002

Quality of sexual life in Parkinson's disease.

Ninety-one consecutive patients with Parkinson's disease (PD) were asked to grade their general satisfaction from life (GSL) and completed the PDQ-39 and the quality of sexual life questionnaire (QoSL-Q). The reliability of the QoSL-Q was 0.74. Satisfaction from sexual life as reflected by the QoSL-Q significantly decreased with aging (P<0.01) and advanced disease (P<0.05). No correlation was found between the PDQ-39 and the QoSL index. The correlation between the PDQ-39 and GSL (r=-0.334) improved by adding the QoSL-Q, as a 9th dimension to the PDQ-39 (r=-0.405). The QoSL-Q is a reliable tool assessed a unique and important dimension not evaluated by the PDQ-39.

Aged↗
PubMed2002

Olanzapine in Huntington's disease.

OBJECTIVES: To study the effect of olanzapine (OL) in Huntington's disease (HD) patients. DESIGN AND METHODS: Eleven HD patients (five men), aged 47.6 +/- 11.4 years and with disease duration of 11.2 +/- 3.3 years received OL. Assessment was carried out using the Clinical Global Impression of Change Scale (CGIC) and the Unified Huntington's Disease Rating Scale behavioral (UHDRS - b) and motor (UHDRS - m) at 6 month intervals. RESULTS: Nine patients were treated for 9.8 +/- 5.9 months. The mean OL dose/patient was 11.4 +/- 8.5 mg/day (median 10 mg/day). Mean CGIC was 2.1 +/- 0.8. UHDRS - b improved significantly (P < 0.0001) and UHDRS - m did not change. Chorea improved in five patients and two dropped out because of drug eruption and lack of efficacy. CONCLUSION: OL is a good alternative treatment in HD, mainly for the psychiatric symptoms and moderately effective for the motor symptoms, possibly because of its effect on chorea. We suggest OL should be used in HD patients with the adult onset form, severe chorea and/or severe psychiatric disturbances.

Adult↗
PubMed2001

Freezing of gait in PD: prospective assessment in the DATATOP cohort.

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.

Aged↗
PubMed2001

The nigrostriatal dopaminergic system in familial early onset parkinsonism with parkin mutations.

Nigrostriatal dopaminergic function and cerebral energy metabolism were measured with PET in two brothers with early-onset parkinsonism caused by mutation of the parkin gene. Energy metabolism did not differ, but the nigrostriatal dopaminergic pattern was clearly different than that of sporadic PD. Thus parkinsonism in these two patients was shown to be pathophysiologically different than PD.

Age of Onset↗
PubMed2001

Gastric emptying time and gastric motility in patients with Parkinson's disease.

Gastrointestinal symptoms such as nausea, abdominal pain, and bloating are frequent complaints of patients with Parkinson's disease (PD). It has been postulated that impaired gastrointestinal function may contribute to the development of motor fluctuations such as delay on and no on in patients with PD. Gastrointestinal impaired function and symptoms may be associated with the disease itself or secondary to levodopa treatment. Thus, we assessed gastric emptying (GE) and gastric motility in PD patients to examine the association between clinical status and gastric function. GE and antral contraction (frequency and amplitude) were evaluated by scintigraphy in 29 patients with mild PD (Hoehn and Yahr [H&Y] stage 1.0-2.0); 22 patients with moderate PD (H&Y stage 2.5-3.0); and 22 healthy volunteers, following the ingestion of a labeled standard meal. Gastric emptying (mean +/- SD of T(1/2)) and antral contraction were not significantly different between patients with mild PD (63.4 +/- 28.8 minutes) and moderate PD (54.7 +/- 25.5 minutes). In the control group, GE was 43.4 +/- 10.8 minutes (range 29.0 - 61.0 minutes). The prevalence of delayed emptying (>61 minutes) was not significantly different in patients with mild disease (48.3%) as compared with patients with moderate disease (36.4%). Antral contraction, both frequency and amplitude, were not significantly different between patients with mild and moderate PD throughout the entire 100 minutes of the study. Untreated patients (n = 28) had mean GE T(1/2) of 59 +/- 30.6 minutes. Patients with smooth response to levodopa showed slower GE (n = 10; 73.6 +/- 25.3 minutes), while treated patients with motor response fluctuations when tested at the on state (n = 13), had much faster GE (49.3 +/- 16.2 minutes). This shortened GE in the on state was similar to the GE of normal volunteers. We conclude that gastric emptying time in patients with PD was delayed compared with control volunteers. It was even slower in patients treated with levodopa. This effect of levodopa treatment was reversed to pseudonormalization (normal GE) at the advanced stages of the disease, when patients developed motor response fluctuation. Other clinical features of PD were not associated with delayed gastric emptying.

Aged↗
PubMed2001

The effect of botulinum toxin injections to the calf muscles on freezing of gait in parkinsonism: a pilot study.

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.

Aged↗
PubMed2001

Clinical characteristics of neuroleptic-induced parkinsonism.

In order to characterize the clinical spectrum of neuroleptic-induced parkinsonism (NIP), we studied a population of consecutive psychiatric in-patients treated with neuroleptics for at least two weeks, who were diagnosed by their psychiatrist as having parkinsonism. Parkinsonism was confirmed by a movement disorders specialist who performed neurological assessment including the motor examination and the activities of daily living (ADL) sections of the Unified Parkinson's Disease Rating Scale (UPDRS), and the Hoehn and Yahr (H&Y) staging. Seventy-five patients (54 males), aged 46 +/- 13 years (range 21 to 73 years) were included in the analysis. The mean duration of neuroleptic therapy was 15 +/- 12 years, while 61% were treated for more than 10 years. Most of the patients (n = 66, 88%) were scored as H&Y stage 2.5 or less. Rest tremor was present in 44% of the patients, and usually persisted in action. Forty-one patients (61%) had symmetrical involvement. Parkinsonian signs were significantly more common and pronounced in the upper in comparison with the lower limbs (p = 0.0001). Gait disturbances were mild and freezing of gait was very rare (n = 2). Neither age nor duration of therapy or their interaction affected the total motor score or any of the motor sub-scores. In conclusion, NIP differs from PD for more bilateral involvement with relative symmetry, and by affecting upper limbs more often than the lower ones. NIP tends to be associated with the triad of bradykinesia, tremor and rigidity while PD tends to involve gait and posture more often. NIP develops unrelated to duration of neuroleptic treatment or age of the patient, suggesting an individual predisposition to blockage of the dopaminergic receptors.

Activities of Daily Living↗
PubMed2001

Synchrony of rest tremor in multiple limbs in parkinson's disease: evidence for multiple oscillators.

Recent evidence points to involvement of central nervous system oscillators in Parkinson's disease (PD) rest tremor. It remains unknown whether one or multiple oscillators cause tremor in multiple limbs. Based on the prediction that multiple oscillators would cause low coherence even with similar average frequency, we studied 22 PD patients using accelerometers on multiple limbs. Records were digitized and spectral analysis was performed. Peak frequencies in the arms, legs, and chin were similar, indicating that biomechanical factors did not determine the frequency. Coherence between different axes of individual accelerometers and between different segments of the same limb was high. However, coherence between tremor in different limbs was low. There was no consistent pattern across patients of ipsi- vs. contralateral predominance of coherence. These data suggest that tremor in PD is generated by multiple oscillatory circuits, which operate on similar frequencies.

Aged↗
PubMed2001

Freezing of gait in patients with advanced Parkinson's disease.

BACKGROUND: Freezing of Gait (FOG) is one of the most disturbing and least understood symptom in advanced stage of Parkinson's disease (PD). The contribution of the underlying pathological process and the antiparkinsonian treatment to the development of FOG are controversial. OBJECTIVE: To study the relationships between clinical features of PD and therapeutic modalities in patients with advanced PD and FOG. METHODS: Consecutive patients with 5 years or more of PD symptoms (n = 172) (99 men) with mean age at symptoms onset of 58.3 +/- 13.2 years and mean symptoms duration of 11.8 +/- 5.6 years were studied. Clinical data were collected during the last office visit through physical examination, detailed history, review of patients' charts, and other documents. A patient was considered as "freezer" if he/she reported recent experience that the legs got stuck to the ground while trying to walk. The presence of dyskinesia, early morning dystonia or significant postural reflex abnormalities were assessed through history and neurological examination. Duration of treatment with antiparkinsonian drugs was calculated from history charts. Chi square and t test were used to compare the patients with and without FOG. Logistic regression was used for the comparison of association between the presence of FOG (dependent variable) disease duration and disease stage (explanatory variables) and duration of treatment with anti-parkinsonian drugs. RESULTS: The study population consisted of 45 patients at Hoehn and Yahr (H&Y) stage 2.5 (26%), 104 patients at stage 3 (60.5%), and 23 patients at H&Y stages 4-5 (13.5%). Ninety one patients (53%) reported FOG at the time of the study. Severity of the disease expressed by H&Y stage at "off" was a significant contributing factor for FOG with a significant trend (z = 4.38, p < 0.0001), as was longer duration of levodopa treatment, and confirmed by FOG using the multivariate logistic regression (p = 0.01 and p = 0.004, respectively). Using a univariate model, longer duration of treatment with dopamine agonists contribute to the appearance of FOG (p = 0.07) while longer duration of amantadine treatment decreased the appearance of FOG (p = 0.09). There was a significant association between FOG and the presence of dyskinesia (p < 0.002), early morning foot dystonia (p < 0.003) and significant postural instability (p < 0.0005). CONCLUSION: FOG is a common symptom in advanced PD. It is mainly related to disease progression and levodopa treatment.

Adult↗
PubMed2001

Gait festination in Parkinson's disease.

Background: Festinating gait (FSG) was first associated with parkinsonism by Sir James Parkinson, in his original essay on "The Shaking Palsy". Its frequency and relation to other parkinsonian features have never been assessed.Objective: To study the relationships between gait festination and other parkinsonian clinical features among patients with Parkinson's disease (PD).Method: During an open lecture to patients with PD who are followed at the Movement Disorders Unit (MDU) of Tel-Aviv Sourasky Medical Center one of us explained verbally and imitated festinating gait on stage. All attending patients with the help of their care-givers or family members, were asked to answer two written questions regarding their own experience with FSG as well as the degree of disability it causes. Clinical information about each patient was taken from his/her chart at the MDU and missing data was completed during the next office visit or from the family physician. Statistical analysis was performed using t-tests for comparison between groups, Chochran-Armitage test for trends and logistic regression to assess the contribution of age of onset, disease duration and disease severity to the development of FSG.Results: Eighty-one PD patients (58 males, mean age 67.5+/-10.7years) answered the FSG questionnaire. Our study population's mean disease duration was 8.5+/-6.4years, mean Hoehn and Yahr (H&Y) clinical stage of 2.6+/-0.8 and mean levodopa dose of 608+/-375mg/day (15 patients were not on levodopa). Twenty-six patients (32.1%) experienced FSG during the previous month and 56% of them reported that FSG was a significant and disabling symptom. FSG was strongly associated with higher stage of H&Y (p<0.001) with a significant trend as the disease progresses (p=0.001) but not with total score in the motor part of the Unified Parkinson's Disease Rating Scale (UPDRS). Longer disease duration was the only clinical factor, which was found to be associated with FSG in the multivariate model. Thirty seven percent (37%) of the patients with FSG reported frequent falls with association between occasional or frequent falls, as reported on the activity of daily living (ADL) part of the UPDRS, and the presence of FSG (p<0.08). There was no association between significant postural reflex abnormalities as rated on the objective part of the UPDRS and the presence of FSG. There was a significant association between the presence of freezing of gait (FOG) as reported in the ADL part of the UPDRS and the presence of FSG (p<0.001) as well as a significant trend towards more frequent FSG in patients with more severe FOG (p<0.001).Conclusion: FSG was clearly associated with longer duration of PD symptoms but not with disease severity as reflected in the motor part of the UPDRS. The relationships between FSG and postural reflexes abnormalities is unclear but it is frequently associated with falls and freezing of gait.

Journal Article↗
PubMed2001

Quantitative anal sphincter EMG in multisystem atrophy and 100 controls.

OBJECTIVE: To evaluate data of quantitative anal sphincter EMG in normal controls and to compare them with patients with multiple system atrophy (MSA). METHODS: Quantitative anal sphincter EMG were performed on 100 normal controls and 11 patients with MSA to characterise EMG data in these two groups. RESULTS: In the normal controls, there was a trend for increased motor unit potential (MUP) amplitude, duration, area, and polyphasicity with advancing age. Patients with MSA exhibited similar MUP size and fibre density. Significant differences were found only in parameters of the recruitment pattern, which were reduced in MSA, with a diminution in the number of active MUPs during rest. CONCLUSIONS: These results may reflect either decreased number of motor cells in Onuf's nucleus without significant consequential reinnervation, or upper motor neuron involvement affecting the anal sphincter in MSA. They further underline the importance of comparative data for age matched controls.

Adolescent↗
PubMed2001

Lesioning the subthalamic nucleus in the treatment of Parkinson's disease.

Ever since it was demonstrated about twenty years ago by two independent groups (Aziz et al. and Bergman et al.) that the cardinal clinical features of MPTP-induced Parkinson's disease (PD) in non-human primate models can be alleviated by lesions of the subthalamic nucleus (STN), this structure has been the focus of interest for functional neurosurgeons involved in the treatment of PD. Initially lesioning and later chronic high frequency stimulation of the STN has become the standard surgical target of akinetic PD. In this brief report we present our experience with 14 STN lesions (8 unilateral and 3 bilateral) confirmed by post-operative imaging. We found significant improvement in OFF rigidity and in ON tremor following unilateral lesions. The major complications were speech disturbance and L-Dopa resistant limb dystonia. Functional disability scores showed inconsistent reduction. There was insufficient data to comment on the significance of bilateral lesions; however, there was a similar pattern of improvement in tremor and speech disturbance. In addition, there was worsening of gait. We comment on the lower degree of improvement in motor scores in our series compared to the few others in recent literature and stress that even in these studies the UPDRS benefits did not translate directly into functional benefit for the patients.

Electrodes, Implanted↗
PubMed2001

Targeting the subthalamic nucleus.

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.

Electric Stimulation Therapy↗