Silvia Honigman

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 Parkinsons 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 T1/2) 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 T1/2 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.

Oral solution of levodopa ethylester for treatment of response fluctuations in patients with advanced Parkinson's disease.

Levodopa ethylester (LDEE), a highly soluble prodrug of levodopa, may overcome the impaired absorption of regular levodopa, due mainly to a combination of levodopas poor solubility and delayed gastric emptying. We conducted a double‐blind, levodopa‐controlled, multicenter study of oral LDEE solution compared with standard levodopa–carbidopa (LD–CD) tablets. Sixty‐two patients with Parkinsons disease who had “delayed on” and “no‐on” subtypes of response fluctuations were randomly assigned for treatment with LDEE–CD or LD–CD 250/25 mg for 4 weeks (phase A). Only the first morning and first post‐lunch dose of LD were replaced. This was followed by a 2‐week extension with a supplementation of carbidopa (25 mg) to each replaced dose (phase B). Patients filled home diaries 2 weeks before and during the trial period in which times of turning on and off for the two doses were reported. In phase A, mean latency to turning on was reduced by 21% (morning dose) and 17% (post‐lunch dose) in the LDEE–CD group. Percentage of no‐on episodes after the post‐lunch dose was decreased by 21% in the LDEE–CD group but increased by 36% in the LD–CD group (P < 0.01). In phase B, LDEE–CD decreased latencies to on after the morning and post‐lunch doses and no‐on episodes after the post‐lunch dose. The beneficial effects of LDEE were supported by the pharmacokinetic data. Results indicate that LDEE solution is beneficial in ameliorating delayed on and no‐on response fluctuations. This effect of LDEE is due to more rapid levodopa absorption.

Normal Pressure Hydrocephalus Associated with Spinal Cord Tumor

Abstract While the association of spinal cord tumor and high‐pressure hydrocephalus is well known, only 5 cases of spinal cord tumor associated with normotensive hydrocephalus have been reported. Two further cases are described here, discussing the possible pathophysiological mechanism. It is suggested that these patients go through a subclinical stage of high‐pressure hydrocephalus and become normotensive later on, a process which might influence the surgical results.

Effect of ropinirole on visuo-motor test in newly diagnosed Parkinson's disease patients

Objectives –  The aim of this study was to assess the sensitivity of the visuo‐motor test (VMT) compared with the Unified Parkinsons Disease Rating Scale (UPDRS) in newly diagnosed Parkinsons disease (PD) patients.

Immunoregulatory effects of interferon-β and interacting cytokines on human vascular endothelial cells implications for multiple sclerosis

Following pre-treatment with a non dspleting antlCD4 mAb (Hl29.18), which induces long-lasting receptor saturation, PUJ mice were fully proGcad from experimental autoimmune encephalomyelitir (EAE) induced by injection of myelin basic protein (MBP). Lymph node cells from antiCM+ YBP-treated mice were specffically unreqonsive to YBP stimulation in vitro and these mice did not develop EAE following MBP re-challange 5 weeks later when the CD4+ cells were no longer coated by the mAb. Moreover, superantigen staphylococcal enterotoxin 6 (SEB) inoculation which rolnduces EAE in MBP kmtunixed mice, failed to activate encephalitogenic T ceils in antiCD4+ MBPtreated mice indkzatlng that 1 IymphocyW tolerance was established. However, MBP m-challenge 16 waeks later, but not SEB treatment, could produce acute EAE in these mice. This obse~~atlon indicates that no memory of the first priming existed at this time, and that new MBP-specific peripheralizad T cell preclNsors had roached the threshold to produce disease after MBP recognition. On the whole, our findings suggest that tre8tment of PUJ mice with non depleting antlCD4 mAb befors MBP challanga Induces MBPspecific hoies in the peripheral CM call repettoire.

Devic's neuromyelitis optica associated with herpes-simplex infection and predominant gray rather than white matter involvement

There is no effective therapy tu przvcnt cxzccrbz tion and mainly progression In Multiple Sclerosis (MS). Examination of the optic neurltls treatment trial after data on patients followed for several years after their first’attack of optic neuritis revealed that randomized to high-dose Intravenous methylprednisolone treatment had a reduced rate of progression to MS (Beck et al, 1993). The exact mechanism for the accelerated recovery is unknown, although metylprednisolone has been shown to decre-ase the IgG synthetic rate. Introduction of intensive immunosupresive therapy is a complex clinical decision specific for each individual MS patient. Minimally 5 years of intensive immunosupresslve therapy in chronic progressive MS patients are necessary to establish beneficial effect of treatment as compared to their pre-treatment neurologip cal finding. Twenty patients with chronic-progresslve MS were treated with methyleprednisolone (Solumedrol, UpJOhn) lg/d for 2 consecutive days every 2 months for next 18 month. Severe form were treated with intravenous cyclophosphamlde lg/d, only 1 day, too. The mathing procedur took into consideration the following clinical factors: age, dlssease duration, duration progressive stadium and Kurtzke EDSS score.lB-month study period is very short to unamblguos COnclUSlOn. Patients who appeared to do best were younger, with shortes total disease duration. Stabilization progressive form MS for 12 to 18 months 1st the most reasonable goal in the more 0~1. timistlc data and In this therapy we succeeded.