Parkinson Disease: Morgan JC

Mehta SH, Morgan JC, Sethi KD. · Movement Disorders Program, Department of Neurology, Medical College of Georgia, 1429 Harper Street, HF-1121, Augusta, GA 30912, USA. · Curr Neurol Neurosci Rep. · Pubmed #18590613 No free full text.

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.

Mehta SH, Morgan JC, Sethi KD. · Movement Disorders Program, Department of Neurology, Medical College of Georgia, Augusta, GA 30912, USA. · CNS Spectr. · Pubmed #18323761 links to  free full text

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.

Morgan JC, Sethi KD. · Movement Disorders Program, Department of Neurology, Medical College of Georgia,1429 Harper Street, HF-1121 Augusta, GA 30912, USA. · Expert Rev Neurother. · Pubmed #17009915 No free full text.

Abstract: Dopaminergic therapies, including levodopa and dopamine agonists, are the mainstays of therapy in Parkinson's disease. With the exception of the injectable short-acting dopamine agonist apomorphine, there is no other widely available non-oral dopaminergic therapy. Rotigotine is a lipid-soluble, non-ergot, D3, D2, D1 dopamine receptor agonist that has demonstrated efficacy as an alternative therapeutic option in both early and advanced Parkinson's disease. More importantly, it is uniquely formulated as a transdermal patch delivery system allowing for continuous, once-daily administration and better patient compliance. Preclinical and clinical trials have shown rotigotine to be a well-tolerated and effective treatment for early-stage Parkinson's disease. Rotigotine has also shown promise as adjunctive therapy with levodopa for the treatment of advanced Parkinson's disease.

Morgan JC, Sethi KD. · Medical College of Georgia, Movement Disorders Program, Department of Neurology, 1429 Harper Street, HF-1121, Augusta, GA 30912, USA. · Expert Opin Emerg Drugs. · Pubmed #16939381 No free full text.

Abstract: Parkinson's disease (PD) afflicts millions of people worldwide. There are numerous drugs available for PD; however, levodopa remains the gold standard of pharmacotherapy to which all other therapies are compared. Levodopa is quite effective for many motor symptoms (bradykinesia, tremor, rigidity) of PD; however, non-levodopa-responsive motor symptoms (postural instability) and nonmotor symptoms are frequently the most troublesome in middle and later stages of disease. Although motor symptoms remain an important focus for emerging drugs, current research is largely geared to identify and develop disease-slowing therapies. Another important area of focus has become treatment of the nonmotor symptoms of PD (especially depression and dementia). This review discusses emerging drugs in the management of the motor and nonmotor symptoms of PD and drugs under study as disease-slowing/neuroprotective agents.

Morgan JC, Sethi KD. · No affiliation provided · Curr Neurol Neurosci Rep. · Pubmed #15217540 No free full text.

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Morgan JC, Sethi KD. · No affiliation provided · Curr Neurol Neurosci Rep. · Pubmed #15217539 No free full text.

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Mehta SH, Prakash R, Prisant LM, Isales CM, Morgan JC, Williams H, Sethi KD. · Movement Disorders Program, Department of Neurology, Medical College of Georgia, 1429 Harper Street, Augusta, GA 30912, USA. · Nat Rev Neurol. · Pubmed #19498437 No free full text.

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.

Ho B, Prakash R, Morgan JC, Sethi KD. · Tufts-New England Medical Center Department of Neurology, USA. · Nat Clin Pract Neurol. · Pubmed #17805247 No free full text.

Abstract: BACKGROUND: 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. INVESTIGATIONS: Video-recorded neurological examinations when in 'off' and 'on' states, brain MRI scan. DIAGNOSIS: Advanced Parkinson's disease complicated by levodopa-responsive camptocormia. MANAGEMENT: Adjustment of dopaminergic therapy (carbidopa-levodopa and entacapone) to minimize motor fluctuations and camptocormia.

Matsukawa N, Maki M, Yasuhara T, Hara K, Yu G, Xu L, Kim KM, Morgan JC, Sethi KD, Borlongan CV. · Department of Neurology, Medical College of Georgia, Augusta, GA 30912, USA. · Brain Res. · Pubmed #17573046 No free full text.

Abstract: Ropinirole, which is a non-ergot dopamine agonist derivative, exerts therapeutic benefits in Parkinson's disease (PD). Based on recent studies implicating dopamine receptors 2 and 3 (D2R and D3R) as possible targets of ropinirole, we over-expressed these dopamine receptor genes in the dopamine-denervated striatum of rodents to reveal whether their over-expression modulated ropinirole activity. Adult Sprague-Dawley rats initially received unilateral 6-hydroxydopamine lesion of the medial forebrain bundle. At 1 month after surgery, successfully lesioned animals (3 or less forelimb akinesia score, and 8 or more apomorphine-induced rotations/min over 1 h) were randomly assigned to intrastriatal injection (ipsilateral to the lesion) of blank lentiviral vector, D2R, D3R or both genes. At about 5 months post-lesion, ropinirole (0.2 mg/kg, i.p.) was administered daily for 9 consecutive days. The subtherapeutic dose of ropinirole improved the use of previously akinetic forelimb and produced robust circling behavior in lesioned animals with striatal over-expression of both D2R and D3R compared to lesioned animals that received blank vector. In contrast, the subtherapeutic dose of ropinirole generated only modest motor effects in lesioned animals with sole over-expression of D2R or D3R. Western immunoblot and autoradiographic assays showed enhanced D2R and D3R protein levels coupled with normalized D2R and D3R binding in the ventral striatum of lesioned animals with lentiviral over-expression of both D2R and D3R relative to vehicle-treated lesioned animals. Immunohistochemical analyses showed that D2R and D3R GFP fluorescent cells colocalized with enkephalin and substance P immunoreactive medium spiny neurons. These data support the use of the subtherapeutic dose of ropinirole in a chronic model of PD.

Morgan JC, Sethi KD. · Movement Disorders Program, National Parkinson Foundation Center of Excellence, Department of Neurology, Medical College of Georgia, Augusta, GA, USA. · Clin Neuropharmacol. · Pubmed #17272971 No free full text.

Abstract: Impaired gastrointestinal motility and constipation are common problems in Parkinson disease (PD). Many patients with PD continue to experience constipation, despite multiple interventions (dietary modification, bulk-forming agents, stool softeners, and laxatives). Tegaserod is a 5-hydroxytryptamine type 4 agonist that stimulates gastrointestinal motility and is approved for the treatment of chronic idiopathic constipation. We report our experience with tegaserod in 5 patients with PD-associated constipation. Tegaserod was well tolerated and improved both bowel movement frequency and stool consistency in most of our patients. Further trials with tegaserod are warranted in PD-associated constipation.

Morgan JC, Sethi KD. · Movement Disorders Program, Department of Neurology, Medical College of Georgia, 1429 Harper Street, HF-1121, Augusta, GA 30912, USA. · Neurology. · Pubmed #16832086 No free full text.

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Sharma P, Morgan JC, Sethi KD. · Movement Disorders Program, Department of Neurology, Medical College of Georgia, Augusta, GA 30912, USA. · Neurology. · Pubmed #16534128 No free full text.

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Iyer SS, Morgan JC, Sethi KD. · Department of Neurology, Medical College of Georgia, Augusta, GA 30912, USA. · Neurology. · Pubmed #16275853 No free full text.

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Iyer SS, Morgan JC, Glover AL, Sethi KD. · Movement Disorders Program, Department of Neurology, Medical College of Georgia, Augusta, Georgia 30912, USA. · Mov Disord. · Pubmed #16001408 No free full text.

Abstract: The presenting manifestations of Parkinson's disease (PD) are variable, but a majority of patients note tremor as the initial symptom. Others complain of slowing of movements, loss of dexterity, fatigue, or changes in handwriting as initial symptoms. We describe a patient who developed an unusual clicking sound emanating from his throat as the initial manifestation of PD.

Morgan JC, Sethi KD. · Department of Neurology, University of Virginia, Charlottesville 22908, USA. · Neurology. · Pubmed #12821767 No free full text.

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Morgan JC, Sethi KD. · No affiliation provided · Arch Neurol. · Pubmed #16533980 No free full text.

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Morgan JC, Iyer SS, Sethi KD. · No affiliation provided · Arch Neurol. · Pubmed #16476826 No free full text.

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Morgan JC, diDonato CJ, Iyer SS, Jenkins PD, Smith JR, Sethi KD. · No affiliation provided · Mov Disord. · Pubmed #16258943 No free full text.

This publication has no abstract.