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Movement Disorders 04/2013; · 4.51 Impact Factor
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ABSTRACT: Restless legs syndrome (RLS), also known as Willis-Ekbom disease, is a common sensorimotor disorder that may be idiopathic (primary) or secondary to a diverse group of conditions. The pathophysiology of primary RLS is only partly understood, but a strong association with brain iron deficiency possibly resulting in impaired dopaminergic function has been recognized. Genomic studies have established a genetic basis for primary RLS as well, and at least 42% of people with primary RLS possess a first-degree relative with the disorder. Secondary RLS is often associated with renal insufficiency, pregnancy, iron deficiency anemia, diabetic neuropathy, and Parkinson's disease. Approximately one-fourth of pregnant women experience RLS, with more intense symptoms experienced during the third trimester, and resolution of symptoms typically occurring within a few months after delivery, though RLS may resolve as early as 2 weeks after delivery. Restless legs syndrome is associated with increased prevalence of mood disturbances, sleep disturbances, and an impaired quality of life. The diagnosis of RLS involves 4 essential criteria related to a compelling urge to move the legs with an accompanying unpleasant sensation in the legs that is worse in the evening and at rest and improved by movement. Treatment of RLS incorporates both pharmacologic and nonpharmacologic approaches. Dopamine agonists are the mainstay of RLS treatment, but other therapies, including gabapentin, benzodiazepines, and low-potency opioids, are also commonly employed.
The American journal of managed care 08/2012; 18(5 Suppl):S83-8. · 2.46 Impact Factor
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ABSTRACT: Biomarkers are objectively measured characteristics that are indicators of normal biological processes, pathogenic processes,
or responses to therapeutic interventions. To date, clinical assessment remains the gold standard in the diagnosis of Parkinson’s
disease (PD) and clinical rating scales are well established as the gold standard for tracking progression of PD. Researchers
have identified numerous potential biomarkers that may aid in the differential diagnosis of PD and/or tracking disease progression.
Clinical, genetic, blood and cerebrospinal fluid (proteomics, transcriptomics, metabolomics), and neuroimaging biomarkers
may provide useful tools in the diagnosis of PD and in measuring disease progression and response to therapies. Some potential
biomarkers are inexpensive and do not require much technical expertise, whereas others are expensive or require specialized
equipment and technical skills. Many potential biomarkers in PD show great promise; however, they need to be assessed for
their sensitivity and specificity over time in large and varied samples of patients with and without PD.
KeywordsBiomarkers-Parkinson’s disease-University of Pennsylvania Smell Identification Test (UPSIT)-8-hydroxydeoxyguanosine (8-OHdG)-Dopamine transporter-Radiotracer neuroimaging-Hoehn and Yahr staging-Unified Parkinson’s Disease Rating Scale (UPDRS)-Transcranial ultrasound-α-Synuclein-Uric acid-Diffusion tensor imaging (DTI)-Proteomics-Metabolomics-Gene expression profiling-REM behavior disorder-Non-Motor Questionnaire and Scale-Leucine-rich repeat kinase-2 (LRRK2)-Glucocerebrosidase-Parkin-Metaiodobenzylguanidine (MIBG)
Current Neurology and Neuroscience Reports 04/2012; 10(6):423-430. · 3.45 Impact Factor
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Movement Disorders 10/2011; 26(12):2178. · 4.51 Impact Factor
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Current Neurology and Neuroscience Reports 11/2010; 10(6):413-6. · 3.45 Impact Factor
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ABSTRACT: Biomarkers are objectively measured characteristics that are indicators of normal biological processes, pathogenic processes, or responses to therapeutic interventions. To date, clinical assessment remains the gold standard in the diagnosis of Parkinson's disease (PD) and clinical rating scales are well established as the gold standard for tracking progression of PD. Researchers have identified numerous potential biomarkers that may aid in the differential diagnosis of PD and/or tracking disease progression. Clinical, genetic, blood and cerebrospinal fluid (proteomics, transcriptomics, metabolomics), and neuroimaging biomarkers may provide useful tools in the diagnosis of PD and in measuring disease progression and response to therapies. Some potential biomarkers are inexpensive and do not require much technical expertise, whereas others are expensive or require specialized equipment and technical skills. Many potential biomarkers in PD show great promise; however, they need to be assessed for their sensitivity and specificity over time in large and varied samples of patients with and without PD.
Current Neurology and Neuroscience Reports 11/2010; 10(6):423-30. · 3.45 Impact Factor
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Movement Disorders 10/2010; 25(13):2260-1. · 4.51 Impact Factor
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Kapil D Sethi
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ABSTRACT: Parkinson disease (PD) is associated with a progressive decline in patient quality of life (QoL), because of motor and nonmotor manifestations of PD and treatment-related side effects.
Treatment with carbidopa/levodopa-the current gold standard therapy-improves QoL in the short term, but gains are not maintained over a long term. Long-term treatment is associated with symptom re-emergence (end-of-dose "wearing off") and development of dyskinesia, which may have an adverse impact on QoL.
Levodopa (LD; combined with carbidopa) remains the gold standard for symptomatic treatment of PD, but long-term treatment is associated with complications that may adversely affect QoL. Recent studies have suggested that the addition of a catechol-O-methyltransferase inhibitor may improve QoL through the reduction of some of the motor complications of LD therapy. Further studies are required to determine the full effects of this as well as other treatments that are used to manage LD-associated complications on QoL.
The Neurologist 03/2010; 16(2):76-83. · 1.26 Impact Factor
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Current Neurology and Neuroscience Reports 08/2009; 9(4):266-7. · 3.45 Impact Factor
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ABSTRACT: Neurologic paraneoplastic syndromes (NPSs) result from damage to the nervous system due to the remote effects of cancer not related to metastasis, infection, or metabolic derangements. NPSs are rare, affecting 1 in 10,000 patients with cancer. Pathogenesis is likely related to the immune mechanisms: normal neural tissue is mistakenly attacked due to the similarity in the onconeural antigens expressed by the tumor cells. Among the various "classic" and other NPSs, this review focuses on paraneoplastic movement disorders, including ataxia due to cerebellar degeneration, stiff-person syndrome, opsoclonus-myoclonus syndrome, chorea, parkinsonism, and tremor. The recently described syndrome of paraneoplastic anti-N-methyl-D-aspartate receptor encephalitis is also included, given that these patients have complex movements such as stereotypies and dyskinesias in addition to psychiatric symptoms, altered sensorium, and other neurologic signs. Although variable, treatment and prognosis of NPSs rely heavily on treatment of the underlying malignancy and immunotherapy.
Current Neurology and Neuroscience Reports 08/2009; 9(4):285-91. · 3.45 Impact Factor
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ABSTRACT: BACKGROUND: A 59-year-old man with a 7-year history of Parkinson disease (PD) presented with episodes of sudden, severe headaches with neck pain, tachycardia, sweating and pallor. During these episodes, the patient showed marked elevations in blood pressure, regardless of posture. This was unusual, given that he had no prior history of hypertension. The array of symptoms raised suspicions of pheochromocytoma, but diagnosis was challenging, as the standard diagnostic biochemical tests were confounded by dopaminergic medications. Further work-up revealed left adrenal medullary hyperplasia. Several reports exist of pseudopheochromocytoma in patients on dopaminergic therapy, but this is the first documented case of pheochromocytoma syndrome due to adrenal medullary hyperplasia in a patient with PD. This case highlights the challenges of performing a diagnostic work-up in a PD patient with symptoms suggestive of pheochromocytoma, and illustrates the utility of (123)I-metaiodobenzylguanidine ((123)I-MIBG) single-photon emission CT in making a diagnosis.Investigations. Physical examination, laboratory tests, abdominal MRI scan, abdominal (123)I-MIBG scan, abdominal (18)F-fluorodeoxyglucose PET scan. DIAGNOSIS: Pheochromocytoma syndrome due to adrenal medullary hyperplasia.Management. Surgical excision of the left adrenal gland.
Nature Reviews Neurology 07/2009; 5(6):343-7. · 12.46 Impact Factor
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ABSTRACT: Paroxysmal dyskinesias are a rare group of movement disorders affecting both adults and children. Based on the events that precipitate the abnormal movements, they are subdivided into paroxysmal kinesigenic dyskinesia (PKD), precipitated by sudden voluntary movements; paroxysmal nonkinesigenic dyskinesia (PNKD), which occurs at rest; paroxysmal exertion-induced dyskinesia (PED), occurring after prolonged exercise; and paroxysmal hypnogenic dyskinesia (PHD), which occurs in sleep. Paroxysmal dyskinesias can be sporadic, familial (autosomal dominant inheritance), or secondary to other disorders. Recent genetic discoveries may aid us in elucidating the pathophysiology of these disorders. PKD has been linked to the pericentromeric region of chromosome 16, PNKD is associated with mutations in the myofibrillogenesis regulator 1 (MR-1) gene on the long arm of chromosome 2 (2q32-36 locus), and PED is associated with mutations in the glucose transporter gene, GLUT1, responsible for glucose transport across the blood-brain barrier. Lifestyle modification to avoid precipitating factors is important in the management of paroxysmal dyskinesias. Medical therapies have not been examined in controlled trials. Nevertheless, anticonvulsants have been found to be extremely effective in treating PKD and are sometimes useful in other types, suggesting that these disorders may indeed represent forms of channelopathies. Drugs such as acetazolamide, anticholinergics, levodopa, and tetrabenazine have been inconsistently successful. In rare cases with medically refractory symptoms, deep brain stimulation has also been employed. Development of successful treatments for the different paroxysmal dyskinesias rests on elucidating the pathophysiology and targeting therapy to treat the underlying perturbation.
Current Treatment Options in Neurology 06/2009; 11(3):170-8. · 1.29 Impact Factor
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10/2008: pages 345 - 352; , ISBN: 9780470713990
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Current Neurology and Neuroscience Reports 08/2008; 8(4):279-80. · 3.45 Impact Factor
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ABSTRACT: Parkinson's disease is a progressive, widespread, neurodegenerative disease in which the involvement of the dopaminergic neurons of the substantia nigra results in significant dopamine depletion in the striatum. Newer imaging modalities reviewed here, using various radioligands, positron emission tomography, and single-photon emission computed tomography, have made it possible to assess the in vivo presynaptic and postsynaptic dopaminergic function. This is not only important from a diagnostic standpoint; these tests are being increasingly studied as surrogate markers to assess disease progression and responses to various interventions, including drugs. A brief comment on their role as a putative biomarker of the disease is also included. Because Parkinson's disease involves multiple neurotransmitter systems, neuroimaging of neurotransmitter systems other than dopamine is also discussed. Lastly, the evidence supporting the use of transcranial ultrasonography and substantia nigra hyperechogenicity in the diagnosis of Parkinson's disease is presented, along with some controversies that surround this technique.
Current Neurology and Neuroscience Reports 08/2008; 8(4):297-303. · 3.45 Impact Factor
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Journal of neurology, neurosurgery, and psychiatry 08/2008; 79(8):964-5. · 4.87 Impact Factor
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ABSTRACT: Sleep dysfunction is common among patients with Parkinson's disease and occurs in approximately two thirds of patients. The problems range from nocturnal issues such as difficulty with sleep initiation, sleep fragmentation, disturbance of circadian rhythm, and rapid eye movement sleep behavior disorder, to daytime problems such as excessive daytime sleepiness. Frequent nighttime awakening and sleep disruption are the most common sleep problems in Parkinson's disease. Dopamine plays an important role in maintaining wakefulness. To improve sleep in Parkinson's disease, it is important to achieve the critical balance of adequate dopaminergic therapy and control of symptoms. Increased dopaminergic agents can cause dyskinesias and painful dystonia, and undertreatment can cause nighttime akinesia, rigidity, and worse quality of sleep. Other nondopaminergic drugs commonly used in Parkinson's disease can also affect sleep. In patients with advanced Parkinson's disease, deep brain stimulation of the subthalamic nucleus has a favorable impact on sleep quality and sleep architecture.
CNS spectrums 04/2008; 13(3 Suppl 4):6-11. · 2.20 Impact Factor
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[show abstract]
[hide abstract]
ABSTRACT: Parkinson’s disease is a progressive, widespread, neurodegenerative disease in which the involvement of the dopaminergic neurons
of the substantia nigra results in significant dopamine depletion in the striatum. Newer imaging modalities reviewed here,
using various radioligands, positron emission tomography, and single-photon emission computed tomography, have made it possible
to assess the in vivo presynaptic and postsynaptic dopaminergic function. This is not only important from a diagnostic standpoint;
these tests are being increasingly studied as surrogate markers to assess disease progression and responses to various interventions,
including drugs. A brief comment on their role as a putative biomarker of the disease is also included. Because Parkinson’s
disease involves multiple neurotransmitter systems, neuroimaging of neurotransmitter systems other than dopamine is also discussed.
Lastly, the evidence supporting the use of transcranial ultrasonography and substantia nigra hyperechogenicity in the diagnosis
of Parkinson’s disease is presented, along with some controversies that surround this technique.
Current Neurology and Neuroscience Reports 01/2008; 8(4):297-303. · 3.45 Impact Factor
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ABSTRACT: Parkinson's disease (PD) afflicts millions of people worldwide and leads to cognitive impairment or dementia in the majority of patients over time. Parkinson's disease dementia (PDD) is characterized by deficits in attention, executive and visuospatial function, and memory. The clinical diagnostic criteria and neuropathology surrounding PDD remain controversial with evidence of overlap among PDD, dementia with Lewy bodies (DLB) and Alzheimer's disease (AD). Cortical cholinergic deficits are greater in PDD than in AD, and are well-correlated with the cognitive and neuropsychiatric dysfunction that occurs in PDD. Inhibition of acetylcholine metabolism is therefore a practical therapeutic strategy in PDD.This review examines current evidence for rivastigmine (a cholinesterase/butyrylcholinesterase inhibitor) treatment in PDD. In addition to its efficacy, we examine the safety profile, side effects, and cost effectiveness of rivastigmine in PDD. Rivastigmine provides modest benefit in PDD and further long-term studies are needed to determine the effectiveness and safety of rivastigmine over time. Tolerability is a problem for many PDD patients treated with rivastigmine. Future studies of rivastigmine in PDD should focus on pragmatic outcomes such as time to need for nursing home placement, pharmacoeconomic outcomes and simultaneous patient/caregiver quality of life assessments.
Neuropsychiatric Disease and Treatment 01/2008; 3(6):775-83. · 1.81 Impact Factor
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ABSTRACT: A 48-year-old man with a 9-year history of Parkinson's disease who had previously shown a good response to levodopa presented for evaluation of increasingly disabling motor fluctuations and marked camptocormia.
Video-recorded neurological examinations when in 'off' and 'on' states, brain MRI scan.
Advanced Parkinson's disease complicated by levodopa-responsive camptocormia.
Adjustment of dopaminergic therapy (carbidopa-levodopa and entacapone) to minimize motor fluctuations and camptocormia.
Nature Clinical Practice Neurology 10/2007; 3(9):526-30. · 7.64 Impact Factor
