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PurposeStudies of pregabalin for the treatment of central neuropathic pain have been limited to double-blind trials of 4–17 weeks in duration. The purpose of this study was to assess the long-term safety and tolerability of pregabalin in Japanese patients with central neuropathic pain. The efficacy of pregabalin was also assessed as a secondary measure.Patients and methodsThis was a 53-week, multicenter, open-label trial of pregabalin (150–600 mg/day) in Japanese patients with central neuropathic pain due to spinal cord injury, multiple sclerosis, or cerebral stroke.ResultsA total of 103 patients received pregabalin (post-stroke =60; spinal cord injury =38; and multiple sclerosis =5). A majority of patients (87.4%) experienced one or more treatment-related adverse events, most commonly somnolence, weight gain, dizziness, or peripheral edema. The adverse event profile was similar to that seen in other indications of pregabalin. Most treatment-related adverse events were mild (89.1%) or moderate (9.2%) in intensity. Pregabalin treatment improved total score, sensory pain, affective pain, visual analog scale (VAS), and present pain intensity scores on the Short-Form McGill Pain Questionnaire (SF-MPQ) and ten-item modified Brief Pain Inventory (mBPI-10) total score at endpoint compared with baseline. Improvements in SF-MPQ VAS and mBPI-10 total scores were evident in all patient subpopulations. Mean changes from baseline in SF-MPQ VAS and mBPI-10 scores at endpoint were −20.1 and −1.4, respectively.ConclusionThese findings demonstrate that pregabalin is generally well tolerated and provides sustained efficacy over a 53-week treatment period in patients with chronic central neuropathic pain.

Clinical symptoms of Parkinson's disease (PD) include not only motor distress but also autonomic dysfunction. Orthostatic hypotension (OH) occurs in one-fifth to one-half of all patients with PD. We examined the relation of this type of hypotension to clinical features and cardiovascular parameters such as cardiac 123I-meta-iodobenzylguanidine (MIBG) uptake, changes on the Valsalva maneuver, and plasma norepinephrine concentrations on head-up tilt-table testing (HUT). We performed HUT in 55 patients with PD and divided them into two groups according to the presence or absence of OH, defined as a drop in systolic blood pressure (SBP mmHg) by 20 mmHg or more on standing. We evaluated cardiac sympathetic function by 123I-MIBG scintigraphy and assessed cardiovascular autonomic function by using the Valsalva maneuver in all subjects. We also performed HUT, 123I-MIBG scintigraphy and assessed cardiovascular autonomic function by using the Valsalva maneuver in 20 controls. The results of HUT showed that 20 patients had OH and 35 did not. The hypotension was associated with gender, older age, longer disease duration, posture and gait instability phenotype, low mini-mental state examination scores and visual hallucinations. Cardiac 123I-MIBG uptakes were lower in patients with OH. SBP fell further during early second phase in patients with OH than in patients without the condition and their increase in SBP during the late second phase and the overshoot of SBP during the fourth phase were lower. The blood pressure recovery time during the fourth phase on the Valsalva maneuver was longer in patients with OH than in those without OH. There was, however, no association between the fall in SBP on HUT and baroreflex sensitivity or the plasma norepinephrine concentrations, adjusted by age, disease duration, disease severity and dopaminergic medication using multiple regression analyses. Patients without OH already had impaired cardiac sympathetic and baroreceptor reflex functions as early abnormalities of cardiovascular autonomic control. Our results suggest that pronounced vasomotor and cardiac sympathetic dysfunction is the primary cause of OH in PD, although baroreceptor reflex failure may also make a minor contribution. It was unclear whether vasomotor and cardiac sympathetic dysfunction in patients with PD was caused primarily by the impairment of preganglionic or postganglionic lesions.

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Background: The image diagnosis of idiopathic normal-pressure hydrocephalus (iNPH) is based on the ventriculomegaly, whose criterion is an Evans' Index (EI) >0.3. Recently, disproportionately enlarged subarachnoid space hydrocephalus (DESH) has been proposed as a morphological characteristic to iNPH. Several studies cast doubt on the reliability of these criteria in the diagnosis of iNPH. Furthermore, interobserver differences of these criteria have not yet been investigated. The objective of this study was to assess the diagnostic reliability and interobserver variability of EI and DESH. Materials and Methods: The preoperative magnetic resonance (MR) images of 84 definite iNPH patients were retrospectively evaluated by a neuroradiologist (NR) and physical therapist (PT). They independently assessed the EI and DESH. The MR images were evaluated preoperatively by a neurosurgeon (NS). The results were showed in mean (standard deviation). Results: The mean age was 78.4 (6.3) years (male:female = 49:35). The mean EI was 0.33 (0.04), 0.32 (0.04), and 0.31 (0.03) for NS, NR, and PT, respectively (P < 0.0001). The rate of accurate diagnosis of iNPH with EI >0.3 was 74%, 66%, and 61% for NS, NR, and PT, respectively, and there was a moderate level of agreement. By contrast, there was a substantial lower level of accuracy in assessment with DESH for all three evaluators as 50%, 44%, and 27% for NS, NR, and PT, respectively, again with a moderate level of agreement. However, the rates of patients fulfilling both EI >0.3 and DESH were remarkably lower than either of the two parameters individually at a mere 37%, 30%, and 16% for NS, NR, and PT, respectively, with a low level of agreement between the rates. Conclusion: This study suggests that DESH cannot be a diagnostic criterion for iNPH. If EI >0.3 and DESH were both necessary to diagnose iNPH, then more than 70% of patients would have been misdiagnosed and would have been deprived of the chance of treatment and its benefits. These results request a paradigm shift in the concepts of iNPH.