Professor neurology Nyu barrow neurological institute emeritusLonnie and Muhammad Ali professor Parkinson Disease retiredExpert on Adolf Hitler’s Parkinson disease Muhammad Ali Doctor for 30 years
A hypothesis is proposed that (a) the skeletomotor basal ganglia-thalamocortical loop functions a... more A hypothesis is proposed that (a) the skeletomotor basal ganglia-thalamocortical loop functions as a model of the behavior of the body and the environment, and that (b) dopaminergic neurons of the substantia nigra pars compacta comprise the substrates of an error distribution system projecting to the striatum. This error signal initiates the learning process in the basal ganglia - learning starts with increasing intensity of the error signal and is complete when the signal is minimized. Parkinson's disease (PD) may be considered as a disruption of learning processes in the basal ganglia that results from progressive degeneration of the substrate that is the error distribution system for this functional motor loop. Numerous clinical and experimental observations obtained from functional procedures for PD that show identical clinical effects in alleviating parkinsonian symptoms, e.g. thermocoagulative lesions and chronic stimulation, can be explained through the use of this conceptual theory of basal ganglia function. Because any controlling neural network must possess a model of the behavior of its controlled object, the heuristics outlined in this theory are broadly applicable for explaining the function of the nervous system, as well as being useful for planning surgical procedures and future strategies in functional neurosurgery.
We present a patient with Parkinson's disease whose bilateral tremor transiently resolved... more We present a patient with Parkinson's disease whose bilateral tremor transiently resolved after a unilateral left ventrolateral thalamotomy. The transient resolution of the bilateral tremor was associated with a focal thalamic lesion and a second lesion in the corpus callosum. The mechanism of this phenomenon may be related to temporary disruption of descending bilateral corticostriate projections by the callosal lesion.
We describe clinical, echocardiographic, and catheterization findings that were present initially... more We describe clinical, echocardiographic, and catheterization findings that were present initially and during therapy in a myxedematous patient with a large pericardial effusion and tamponade. Treatment with thyroxine resulted in a marked improvement of most of the clinical features of hypothyroidism and some improvement in cardiac function. However, the pericardial effusion as well as clinical and laboratory evidence of tamponade persisted for 2 months after full replacement doses of T4 had been achieved. The tamponade was finally relieved by fenestration of the parietal pericardium. These findings are consistent with evidence of an abnormality of pericardial drainage that persists for months after other thyroid hormone dependent functions are normalized by thyroxine replacement. Therefore prompt surgical drainage rather than dependence on medical therapy alone is indicated in myxedematous patients who have cardiac tamponade.
OBJECTIVE: To study the effect of variable deep brain stimulation frequencies on balance and gait... more OBJECTIVE: To study the effect of variable deep brain stimulation frequencies on balance and gait in patients with either bilateral Subthalamic nucleus(STN)or Globus pallidus internus (GPi)deep brain stimulator: A quantitative analysis. BACKGROUND:Gait and balance abnormalities are major contributor to falls in Parkinson Disease(PD)patients. Recent study indicates that low-frequency stimulation of STN or GPi improve gait in PD. In this study we quantitatively studied the effect of Low (LF-30Hz), intermediate (IF-80 HZ) and high frequency ( HF- clinically determined)DBS of STN and GPi METHODS: We tested 10 patients (5 STN and 5 GPi). Subjects were first tested in their usual HF DBS settings. They were reevaluated twice at IF, and LF conditions in off-medications state after random selection of the sequence. Minimum of 30-minute wait period was allowed before evaluation after changing stimulation frequency.Quantitative gait parameters were obtained using Mobilty Lab portable gait syatem sensors. Motor impairements were tested using Unified Parkinson9s Disease Rating scale (UPDRS). Gait measure include stride length, speed, cadence, step duration, double support. Arm swing velocity, number of steps and turning duration. Result:Stride length improved in 5 patients on IF, 4 patients on HF and 1 patient on LF. Double support duration improved in 4 patients on IF, 3 patients on HF and 3 patients on LF. Cadence improved in 4 patients on IF, 3 patients on HF and 3 patients in LF stimulation. Gait stride velocity improved in 4 patients on IF and 4 patients on HF and 2patients on LF stimulation. CONCLUSIONS:The motor performance including gait and Balance deteriorated when the frequency of stimulation was changed from high-frequency to Intermediate(80Hz)or low frequency (30HZ). This clearly indicated by increase in UPDRS motor score. With respect to gait measures, in general, the lower frequency (30Hz) stimulation worsened gait and turning easures more than intermediate frequency Disclosure: Dr. Deep has nothing to disclose. Dr. Lieberman has nothing to disclose. Dr. Dhall has received personal compensation for activities with Impax, Merz Pharma, Acadia, Medtronic, and IO Therapeutics as a consultant and for activities with Impax, UCB Pharma, Teva Neuroscience as a speaker. Dr. Shafer has nothing to disclose. Dr. Tateuchi has nothing to disclose. Dr. Simpson has nothing to disclose. Dr. Frames has nothing to disclose.
Publisher Summary This chapter examines the adrenal medullary transplants as a treatment for adva... more Publisher Summary This chapter examines the adrenal medullary transplants as a treatment for advanced Parkinson's disease (PD). In a study described in the chapter, patients selected for autologous adrenal medullary to caudate nucleus transplantations were patients with advanced PD who were no longer responding satisfactorily to antiparkinson medication. Prior to surgery, all 12 patients were assessed using the Unified Parkinson Disease Rating Scale (UPDRS). All patients were assessed on the UPDRS both in an “on” and an “off” period. The first 6 patients were operated through a right frontal craniotomy. The next 6 patients were operated through a transcallosal approach. The adrenal medullary and caudate tissues were assayed for tyrosine hydroxylase (TH) activity, and the caudate tissue was assayed for homovanillic acid (HVA) and dihydroxyphenylacetic acid (DOPAC). The results of the surgery for the group revealed 35% reduction in L-dopa (which was always combined with carbidopa), a 13% reduction in the patient's stage in the “off” period, and a 30% reduction in the fluctuation score subset of the UPDRS.
The Distribution of Monoamine Oxidases A and B in Normal Human Brain, Karin N. Westlund Effects o... more The Distribution of Monoamine Oxidases A and B in Normal Human Brain, Karin N. Westlund Effects of Disease and Aging on Monoamine Oxidases A and B, Manfred Gerlach, Peter Riederer, and Moussa B. H. Youdim Biochemistry and Mechanism of Action of Monoamine Oxidases A and B, Eimear M. O'Brien and Keith F. Tipton The Structure, Gene, and Promoter Organization of Monoamine Oxidases A and B, Jean Chen Shih, Kevin Chen, Joseph S. Grimsby, Qin-Shi Zhu, and Timothy K. Gallaher Molecular Genetics and Inheritance of Human Monoamine Oxidases A and B, Xandra O. Breakefield, Zheng-Yi Chen, Elizabeth Tivol, Christo Shalish, and Ian W. Craig Role of Monoamine Oxidase Genetics in the Etiology of Parkinson's Disease, Janice H. Kurth and Matthias C. Kurth Multiple Forms of Monoamine Oxidase and Iron: Their Relevance to the Pathology and Treatment of Parkinson's Disease, Moussa B. H. Youdim, Dorit Ben-Shachar, and Peter Riederer A Critical Role for Monoamine Oxidase in Toxin Action in Parkinson's Disease, Peter Jenner Effects of Monoamine Oxidase B Inhibitors on Dopaminergic Function: Role of 2-Phenylethylamine and Aromatic L-Amino Acid Decarboxylase, Augusto V. Juorio, Xin-Min Li, I. A. Paterson, and Alan A. Boulton Inhibition of Monoamine Oxidase B and the Neuroprotective Effects of Selegiline, Kevin T. Finnegan Reduction of Nerve Cell Death by Deprenyl Without Monoamine Oxidase Inhibition, William G. Tatton, Nadine A. Seniuk, William Y. H. Ju, and Karen S. Ansari Monoamine Oxidase Inhibitors as Neuroprotective Therapy, Warren Olanow and Donald B. Calne Selegiline as Symptomatic Treatment for Parkinson's Disease, Abraham Lieberman Monoamine Oxidase Inhibitors in Alzheimer's Disease, Jody Corey-Bloom and Leon J. Thal Role of Monoamine Oxidase Inhibitors in Psychiatry, David J. Houlihan and Samuel Gershon
New concepts about the pathogenesis and pathophysiology of Parkinson's disease have emerg... more New concepts about the pathogenesis and pathophysiology of Parkinson's disease have emerged. For these concepts to be useful, they must be understood, and for them to be applied, the psychology of the patient and the patient's family must be understood. The initial consultation is crucial in establishing a successful relationship between a patient, family, and physician. This consultation is analyzed and ways of avoiding errors and misconceptions delineated. Emphasis is placed on imaginitive questioning using the format of the ADL portion of the UPDRS in establishing the diagnosis and following treatment. The rational for starting treatment with selegiline at this time is discussed in the context of the role that increased MAO-B activity plays in the progression of Parkinson's disease. After making the diagnosis and starting treatment with selegiline, deciding when to start levodopa is the next crucial decision. Often as important as deciding when to start levodopa is overcoming the resistance of the patient to accept this treatment. The next crucial decision occurs after the patient develops response fluctuations on levodopa. A format for assessing the fluctuations is presented, and the merits of different treatments, including selegiline, dopamine agonists (bromocriptine and pergolide), and sustained-release or controlled-release levodopa preparations (Sinemet CR), discussed. The management of patients with depression, sleep problems, and advanced disease including postural instability and mental changes are reviewed.
Diffuse necrosis and autolysis were found in the brains from 6 comatose, respirator-supported pat... more Diffuse necrosis and autolysis were found in the brains from 6 comatose, respirator-supported patients in whom the bolus technique demonstrated no cerebral blood flow during a period exceeding 20 hours prior to cardiac death. When blood flow was insufficient to produce a bolus, there was no evidence of active tissue response to necrosis. In 6 similar patients, when cerebral blood flow was detected by the bolus technique, less extensive necrosis was observed postmortem and there was active tissue response.
Objective: To evaluate the safety and tolerability of NP002 (nicotine bi-tartrate) in Parkinson’s... more Objective: To evaluate the safety and tolerability of NP002 (nicotine bi-tartrate) in Parkinson’s disease (PD), and the effect of NP002 (versus placebo) on levodopa-induced dyskinesia (LIDs), falls, and freezing of gait (FOG). Background: As PD advances, more than 30% of patients experience falls and FOG, which are relatively refractory to levodopa. LIDs also appear. NP002 may be able to reduce falls and LIDs by rapidly stimulating CNS cholinergic receptors without desensitizing cholinergic receptors for long-term use. Design/Methods: A 12- center, double-blind, randomized trial was undertaken in 65 patients with advanced PD. NP002 was administered 4 times/day for 10 weeks beginning at 1 mg every 6 hours, and increasing to 24 mg/day. Patients were assessed using the Unified Dyskinesia Rating Scale (UDysRS), the Lang-Fahn ADL Dyskinesia Scale, and the Unified Parkinson’s Disease Rating Scale (UPDRS). Results: NP002 was safe and well tolerated. Nausea was the main adverse effect. 14 of 35 (40%) of subjects taking NP002 and 3 of 30 (10%) of subjects on placebo experienced a reduction in falls (p=0.0098, Fisher’s test). Additionally, 12 of 35 patients (34%) on NP002 had a significant (p=0.04, Fisher’s test) reduction in FOG compared to 4 (13%) patients on placebo control. The ambulation part of the Unified Dyskinesia Rating Scale improved significantly (46.3% on NP002 vs 8.6% on placebo, p=0.011). Total dyskinesia symptoms measured on the UDysRS were reduced, but not significantly (p=0. 092). Conclusions: NP002, a novel direct cholinergic agonist, improved two relatively refractory symptoms of PD: falls and FOG, while probably reducing LIDs. Disclosure: Dr. Lieberman has nothing to disclose. Dr. Lockhart has nothing to disclose. Dr. Olson has nothing to disclose. Dr. Smith has nothing to disclose. Dr. Frames has nothing to disclose.
Objective: To evaluate the differences in postural stability during neurogenic orthostatic hypote... more Objective: To evaluate the differences in postural stability during neurogenic orthostatic hypotension (NOH) in Parkinson’s disease (PD), specifically looking at the difference between symptomatic and asymptomatic patients. Background: It is well known that PD patients are at an increased risk for falling compared to healthy elderly adults. Although postural instability is a cardinal feature of PD, not all falls can be attributed to this symptom. A large portion of PD patients also develop orthostatic hypotension, which is defined as a drop of 20 mmHg or greater in systolic blood pressure. This study aims to determine the effect of NOH on postural stability in PD. Design/Methods: Twenty-one subjects with PD from Barrow Neurological Institute in Phoenix, Arizona underwent clinical tilt table testing for NOH. Before and after the tilt testing, subjects were asked to stand quietly on a force plate for one minute with their eyes open and then again with their eyes closed. Different postural stability measures were calculated from the center of pressure data during each of the trials. The force plate collected data at 100 Hz. Results: Of the 21 subjects tested, three did not have orthostatic hypotension and were removed from this analysis. The remaining 18 subjects were 73.3 ± 7.5 years old and had been diagnosed with PD for 5.6 ± 5.5 years. No significant differences were found in postural stability between PD patients who did and did not experience symptoms of NOH for both eyes open and eyes closed trials. Conclusions: PD patients’ postural stability is affected during NOH, regardless of whether or not if the patient experiences any symptoms of NOH. Disclosure: Dr. Smith has nothing to disclose. Dr. Frames has nothing to disclose. Dr. Olson has nothing to disclose. Dr. Lockhart has nothing to disclose. Dr. Lieberman has nothing to disclose.
OBJECTIVE: To determine if step length influence falls in Parkinson Disease (PD) patients. BACKGR... more OBJECTIVE: To determine if step length influence falls in Parkinson Disease (PD) patients. BACKGROUND: Falls are major cause of disability in PD. The objective of this study is to determine if short step and slow step velocity can cause falls. DESIGN/METHODS: We did retrospective analysis of 460 PD patients seen at Muhammad Ali Parkinson center. Demographic and clinical information collected include age, duration of PD, medications, Unified Parkinson Disease Rating Scale (UPDRS)scores, gait length and velocity, incidence of freezing of gait, and occurrence of serious fall. Results: Of the PD patients, 204 (50.5[percnt])fell and 200 (49.5[percnt])did not fall. Of the 204 fallers, 71 (34.8[percnt]) fell more than once. Fallers were significantly older than non fallers ( 72.6±5.8 versus 66.9±6.1 years) and fallers had PD significantly longer (9.3±3.7 versus 5.4±2.2 years), significantly higher ( worse)UPDRS motor scores (29.3±10.9 versus 18.9±8.3),significantly higher ( worse)UPDRS axial scores (9.2±3.5 versus 5.1±2.7),significantly shorter steps (0.45± 0.09 versus 0.60±0.13 meter), and slower velocity (0.75±0.21 versus 0.90±0.31 m/s) compared with non fallers. Fallers were also significantly more likely to have freezing of gait ( 21.1[percnt])than non- fallers ( 10.5[percnt]) ( OR, 2.28;95[percnt] Confidence Interval, 1.30-3.99; p<0.004. Among 204 fallers, 84[percnt] were on levodopa and among 200 non-fallers, 80[percnt] were on levodopa. CONCLUSIONS: In our study, fallers took significantly shorter and slower steps than non-fallers. This "cautious" gait may be an inappropriate adaption to impaired balace. Small and short steps may create a "mismatch" between the speed and displacement of the upper versus the lower body, resulting in the upper body "tipping over" and the patient falling. Education, exercise, and gait and balance training that focuses on increasing step length and velocity may reduce falls. Disclosure: Dr. Deep has nothing to disclose. Dr. Lieberman has nothing to disclose. Dr. Shafer has nothing to disclose.
A hypothesis is proposed that (a) the skeletomotor basal ganglia-thalamocortical loop functions a... more A hypothesis is proposed that (a) the skeletomotor basal ganglia-thalamocortical loop functions as a model of the behavior of the body and the environment, and that (b) dopaminergic neurons of the substantia nigra pars compacta comprise the substrates of an error distribution system projecting to the striatum. This error signal initiates the learning process in the basal ganglia - learning starts with increasing intensity of the error signal and is complete when the signal is minimized. Parkinson&#39;s disease (PD) may be considered as a disruption of learning processes in the basal ganglia that results from progressive degeneration of the substrate that is the error distribution system for this functional motor loop. Numerous clinical and experimental observations obtained from functional procedures for PD that show identical clinical effects in alleviating parkinsonian symptoms, e.g. thermocoagulative lesions and chronic stimulation, can be explained through the use of this conceptual theory of basal ganglia function. Because any controlling neural network must possess a model of the behavior of its controlled object, the heuristics outlined in this theory are broadly applicable for explaining the function of the nervous system, as well as being useful for planning surgical procedures and future strategies in functional neurosurgery.
We present a patient with Parkinson&#39;s disease whose bilateral tremor transiently resolved... more We present a patient with Parkinson&#39;s disease whose bilateral tremor transiently resolved after a unilateral left ventrolateral thalamotomy. The transient resolution of the bilateral tremor was associated with a focal thalamic lesion and a second lesion in the corpus callosum. The mechanism of this phenomenon may be related to temporary disruption of descending bilateral corticostriate projections by the callosal lesion.
We describe clinical, echocardiographic, and catheterization findings that were present initially... more We describe clinical, echocardiographic, and catheterization findings that were present initially and during therapy in a myxedematous patient with a large pericardial effusion and tamponade. Treatment with thyroxine resulted in a marked improvement of most of the clinical features of hypothyroidism and some improvement in cardiac function. However, the pericardial effusion as well as clinical and laboratory evidence of tamponade persisted for 2 months after full replacement doses of T4 had been achieved. The tamponade was finally relieved by fenestration of the parietal pericardium. These findings are consistent with evidence of an abnormality of pericardial drainage that persists for months after other thyroid hormone dependent functions are normalized by thyroxine replacement. Therefore prompt surgical drainage rather than dependence on medical therapy alone is indicated in myxedematous patients who have cardiac tamponade.
OBJECTIVE: To study the effect of variable deep brain stimulation frequencies on balance and gait... more OBJECTIVE: To study the effect of variable deep brain stimulation frequencies on balance and gait in patients with either bilateral Subthalamic nucleus(STN)or Globus pallidus internus (GPi)deep brain stimulator: A quantitative analysis. BACKGROUND:Gait and balance abnormalities are major contributor to falls in Parkinson Disease(PD)patients. Recent study indicates that low-frequency stimulation of STN or GPi improve gait in PD. In this study we quantitatively studied the effect of Low (LF-30Hz), intermediate (IF-80 HZ) and high frequency ( HF- clinically determined)DBS of STN and GPi METHODS: We tested 10 patients (5 STN and 5 GPi). Subjects were first tested in their usual HF DBS settings. They were reevaluated twice at IF, and LF conditions in off-medications state after random selection of the sequence. Minimum of 30-minute wait period was allowed before evaluation after changing stimulation frequency.Quantitative gait parameters were obtained using Mobilty Lab portable gait syatem sensors. Motor impairements were tested using Unified Parkinson9s Disease Rating scale (UPDRS). Gait measure include stride length, speed, cadence, step duration, double support. Arm swing velocity, number of steps and turning duration. Result:Stride length improved in 5 patients on IF, 4 patients on HF and 1 patient on LF. Double support duration improved in 4 patients on IF, 3 patients on HF and 3 patients on LF. Cadence improved in 4 patients on IF, 3 patients on HF and 3 patients in LF stimulation. Gait stride velocity improved in 4 patients on IF and 4 patients on HF and 2patients on LF stimulation. CONCLUSIONS:The motor performance including gait and Balance deteriorated when the frequency of stimulation was changed from high-frequency to Intermediate(80Hz)or low frequency (30HZ). This clearly indicated by increase in UPDRS motor score. With respect to gait measures, in general, the lower frequency (30Hz) stimulation worsened gait and turning easures more than intermediate frequency Disclosure: Dr. Deep has nothing to disclose. Dr. Lieberman has nothing to disclose. Dr. Dhall has received personal compensation for activities with Impax, Merz Pharma, Acadia, Medtronic, and IO Therapeutics as a consultant and for activities with Impax, UCB Pharma, Teva Neuroscience as a speaker. Dr. Shafer has nothing to disclose. Dr. Tateuchi has nothing to disclose. Dr. Simpson has nothing to disclose. Dr. Frames has nothing to disclose.
Publisher Summary This chapter examines the adrenal medullary transplants as a treatment for adva... more Publisher Summary This chapter examines the adrenal medullary transplants as a treatment for advanced Parkinson's disease (PD). In a study described in the chapter, patients selected for autologous adrenal medullary to caudate nucleus transplantations were patients with advanced PD who were no longer responding satisfactorily to antiparkinson medication. Prior to surgery, all 12 patients were assessed using the Unified Parkinson Disease Rating Scale (UPDRS). All patients were assessed on the UPDRS both in an “on” and an “off” period. The first 6 patients were operated through a right frontal craniotomy. The next 6 patients were operated through a transcallosal approach. The adrenal medullary and caudate tissues were assayed for tyrosine hydroxylase (TH) activity, and the caudate tissue was assayed for homovanillic acid (HVA) and dihydroxyphenylacetic acid (DOPAC). The results of the surgery for the group revealed 35% reduction in L-dopa (which was always combined with carbidopa), a 13% reduction in the patient's stage in the “off” period, and a 30% reduction in the fluctuation score subset of the UPDRS.
The Distribution of Monoamine Oxidases A and B in Normal Human Brain, Karin N. Westlund Effects o... more The Distribution of Monoamine Oxidases A and B in Normal Human Brain, Karin N. Westlund Effects of Disease and Aging on Monoamine Oxidases A and B, Manfred Gerlach, Peter Riederer, and Moussa B. H. Youdim Biochemistry and Mechanism of Action of Monoamine Oxidases A and B, Eimear M. O'Brien and Keith F. Tipton The Structure, Gene, and Promoter Organization of Monoamine Oxidases A and B, Jean Chen Shih, Kevin Chen, Joseph S. Grimsby, Qin-Shi Zhu, and Timothy K. Gallaher Molecular Genetics and Inheritance of Human Monoamine Oxidases A and B, Xandra O. Breakefield, Zheng-Yi Chen, Elizabeth Tivol, Christo Shalish, and Ian W. Craig Role of Monoamine Oxidase Genetics in the Etiology of Parkinson's Disease, Janice H. Kurth and Matthias C. Kurth Multiple Forms of Monoamine Oxidase and Iron: Their Relevance to the Pathology and Treatment of Parkinson's Disease, Moussa B. H. Youdim, Dorit Ben-Shachar, and Peter Riederer A Critical Role for Monoamine Oxidase in Toxin Action in Parkinson's Disease, Peter Jenner Effects of Monoamine Oxidase B Inhibitors on Dopaminergic Function: Role of 2-Phenylethylamine and Aromatic L-Amino Acid Decarboxylase, Augusto V. Juorio, Xin-Min Li, I. A. Paterson, and Alan A. Boulton Inhibition of Monoamine Oxidase B and the Neuroprotective Effects of Selegiline, Kevin T. Finnegan Reduction of Nerve Cell Death by Deprenyl Without Monoamine Oxidase Inhibition, William G. Tatton, Nadine A. Seniuk, William Y. H. Ju, and Karen S. Ansari Monoamine Oxidase Inhibitors as Neuroprotective Therapy, Warren Olanow and Donald B. Calne Selegiline as Symptomatic Treatment for Parkinson's Disease, Abraham Lieberman Monoamine Oxidase Inhibitors in Alzheimer's Disease, Jody Corey-Bloom and Leon J. Thal Role of Monoamine Oxidase Inhibitors in Psychiatry, David J. Houlihan and Samuel Gershon
New concepts about the pathogenesis and pathophysiology of Parkinson&#39;s disease have emerg... more New concepts about the pathogenesis and pathophysiology of Parkinson&#39;s disease have emerged. For these concepts to be useful, they must be understood, and for them to be applied, the psychology of the patient and the patient&#39;s family must be understood. The initial consultation is crucial in establishing a successful relationship between a patient, family, and physician. This consultation is analyzed and ways of avoiding errors and misconceptions delineated. Emphasis is placed on imaginitive questioning using the format of the ADL portion of the UPDRS in establishing the diagnosis and following treatment. The rational for starting treatment with selegiline at this time is discussed in the context of the role that increased MAO-B activity plays in the progression of Parkinson&#39;s disease. After making the diagnosis and starting treatment with selegiline, deciding when to start levodopa is the next crucial decision. Often as important as deciding when to start levodopa is overcoming the resistance of the patient to accept this treatment. The next crucial decision occurs after the patient develops response fluctuations on levodopa. A format for assessing the fluctuations is presented, and the merits of different treatments, including selegiline, dopamine agonists (bromocriptine and pergolide), and sustained-release or controlled-release levodopa preparations (Sinemet CR), discussed. The management of patients with depression, sleep problems, and advanced disease including postural instability and mental changes are reviewed.
Diffuse necrosis and autolysis were found in the brains from 6 comatose, respirator-supported pat... more Diffuse necrosis and autolysis were found in the brains from 6 comatose, respirator-supported patients in whom the bolus technique demonstrated no cerebral blood flow during a period exceeding 20 hours prior to cardiac death. When blood flow was insufficient to produce a bolus, there was no evidence of active tissue response to necrosis. In 6 similar patients, when cerebral blood flow was detected by the bolus technique, less extensive necrosis was observed postmortem and there was active tissue response.
Objective: To evaluate the safety and tolerability of NP002 (nicotine bi-tartrate) in Parkinson’s... more Objective: To evaluate the safety and tolerability of NP002 (nicotine bi-tartrate) in Parkinson’s disease (PD), and the effect of NP002 (versus placebo) on levodopa-induced dyskinesia (LIDs), falls, and freezing of gait (FOG). Background: As PD advances, more than 30% of patients experience falls and FOG, which are relatively refractory to levodopa. LIDs also appear. NP002 may be able to reduce falls and LIDs by rapidly stimulating CNS cholinergic receptors without desensitizing cholinergic receptors for long-term use. Design/Methods: A 12- center, double-blind, randomized trial was undertaken in 65 patients with advanced PD. NP002 was administered 4 times/day for 10 weeks beginning at 1 mg every 6 hours, and increasing to 24 mg/day. Patients were assessed using the Unified Dyskinesia Rating Scale (UDysRS), the Lang-Fahn ADL Dyskinesia Scale, and the Unified Parkinson’s Disease Rating Scale (UPDRS). Results: NP002 was safe and well tolerated. Nausea was the main adverse effect. 14 of 35 (40%) of subjects taking NP002 and 3 of 30 (10%) of subjects on placebo experienced a reduction in falls (p=0.0098, Fisher’s test). Additionally, 12 of 35 patients (34%) on NP002 had a significant (p=0.04, Fisher’s test) reduction in FOG compared to 4 (13%) patients on placebo control. The ambulation part of the Unified Dyskinesia Rating Scale improved significantly (46.3% on NP002 vs 8.6% on placebo, p=0.011). Total dyskinesia symptoms measured on the UDysRS were reduced, but not significantly (p=0. 092). Conclusions: NP002, a novel direct cholinergic agonist, improved two relatively refractory symptoms of PD: falls and FOG, while probably reducing LIDs. Disclosure: Dr. Lieberman has nothing to disclose. Dr. Lockhart has nothing to disclose. Dr. Olson has nothing to disclose. Dr. Smith has nothing to disclose. Dr. Frames has nothing to disclose.
Objective: To evaluate the differences in postural stability during neurogenic orthostatic hypote... more Objective: To evaluate the differences in postural stability during neurogenic orthostatic hypotension (NOH) in Parkinson’s disease (PD), specifically looking at the difference between symptomatic and asymptomatic patients. Background: It is well known that PD patients are at an increased risk for falling compared to healthy elderly adults. Although postural instability is a cardinal feature of PD, not all falls can be attributed to this symptom. A large portion of PD patients also develop orthostatic hypotension, which is defined as a drop of 20 mmHg or greater in systolic blood pressure. This study aims to determine the effect of NOH on postural stability in PD. Design/Methods: Twenty-one subjects with PD from Barrow Neurological Institute in Phoenix, Arizona underwent clinical tilt table testing for NOH. Before and after the tilt testing, subjects were asked to stand quietly on a force plate for one minute with their eyes open and then again with their eyes closed. Different postural stability measures were calculated from the center of pressure data during each of the trials. The force plate collected data at 100 Hz. Results: Of the 21 subjects tested, three did not have orthostatic hypotension and were removed from this analysis. The remaining 18 subjects were 73.3 ± 7.5 years old and had been diagnosed with PD for 5.6 ± 5.5 years. No significant differences were found in postural stability between PD patients who did and did not experience symptoms of NOH for both eyes open and eyes closed trials. Conclusions: PD patients’ postural stability is affected during NOH, regardless of whether or not if the patient experiences any symptoms of NOH. Disclosure: Dr. Smith has nothing to disclose. Dr. Frames has nothing to disclose. Dr. Olson has nothing to disclose. Dr. Lockhart has nothing to disclose. Dr. Lieberman has nothing to disclose.
OBJECTIVE: To determine if step length influence falls in Parkinson Disease (PD) patients. BACKGR... more OBJECTIVE: To determine if step length influence falls in Parkinson Disease (PD) patients. BACKGROUND: Falls are major cause of disability in PD. The objective of this study is to determine if short step and slow step velocity can cause falls. DESIGN/METHODS: We did retrospective analysis of 460 PD patients seen at Muhammad Ali Parkinson center. Demographic and clinical information collected include age, duration of PD, medications, Unified Parkinson Disease Rating Scale (UPDRS)scores, gait length and velocity, incidence of freezing of gait, and occurrence of serious fall. Results: Of the PD patients, 204 (50.5[percnt])fell and 200 (49.5[percnt])did not fall. Of the 204 fallers, 71 (34.8[percnt]) fell more than once. Fallers were significantly older than non fallers ( 72.6±5.8 versus 66.9±6.1 years) and fallers had PD significantly longer (9.3±3.7 versus 5.4±2.2 years), significantly higher ( worse)UPDRS motor scores (29.3±10.9 versus 18.9±8.3),significantly higher ( worse)UPDRS axial scores (9.2±3.5 versus 5.1±2.7),significantly shorter steps (0.45± 0.09 versus 0.60±0.13 meter), and slower velocity (0.75±0.21 versus 0.90±0.31 m/s) compared with non fallers. Fallers were also significantly more likely to have freezing of gait ( 21.1[percnt])than non- fallers ( 10.5[percnt]) ( OR, 2.28;95[percnt] Confidence Interval, 1.30-3.99; p<0.004. Among 204 fallers, 84[percnt] were on levodopa and among 200 non-fallers, 80[percnt] were on levodopa. CONCLUSIONS: In our study, fallers took significantly shorter and slower steps than non-fallers. This "cautious" gait may be an inappropriate adaption to impaired balace. Small and short steps may create a "mismatch" between the speed and displacement of the upper versus the lower body, resulting in the upper body "tipping over" and the patient falling. Education, exercise, and gait and balance training that focuses on increasing step length and velocity may reduce falls. Disclosure: Dr. Deep has nothing to disclose. Dr. Lieberman has nothing to disclose. Dr. Shafer has nothing to disclose.
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