Corpus callosum atrophy as a predictor of age-related cognitive and motor impairment: a 3-year follow-up of the LADIS study cohort.

The aim of this 3-year follow-up study was to investigate whether corpus callosum (CC) atrophy may predict future motor and cognitive impairment in an elderly population. On baseline MRI from 563 subjects with age-related white matter changes (ARWMC) from the Leukoaraiosis And DISability (LADIS) study, the CC was segmented and subdivided into five anterior-posterior regions (CC1-CC5). Associations between the CC areas and decline in motor performance and cognitive functions over a 3-year period were analyzed. CC atrophy at baseline was significantly associated with impaired cognitive performance (p<0.01 for CC1, p<0.05 for CC5), motor function (p<0.05 for CC2 and CC5), and walking speed (p<0.01 for CC2 and CC5, p<0.05 for CC3 and total CC), and with development of dementia at 3 years (p<0.05 for CC1) after correction for appropriate confounders (ARWMC volume, atrophy, age, gender and handedness). In conclusion, CC atrophy, an indicator of reduced functional connectivity between cortical areas, seems to contribute, independently of ARWMC load, to future cognitive and motor decline in the elderly.

Battery lifetime in pallidal deep brain stimulation for dystonia.

BACKGROUND AND PURPOSE: The aim of the study was to analyse the lifetime of Soletra implantable pulse generators (IPG) in deep brain stimulation (DBS) of the globus pallidus internus (GPi) for dystonia, depending on stimulation parameters and the total electrical energy delivered (TEED) by the IPG. METHODS: In a prospective series of 20 patients with GPi DBS for dystonia, we recorded IPG longevity and stimulation parameters over time. An evaluation of the TEED was performed using the previously suggested equation [(voltage(2) × pulse width × frequency)/impedance] × 1 s. RESULTS: During median follow-up of 57 months (range 23-79 months), 64 IPGs were replaced because of battery depletion or end of life signal. We found a mean IPG longevity of 25.1 ± 10.1 (range 16-60) months, which was inversely correlated with the TEED (r = -0.72; P < 0.001). IPG longevity was not different between bipolar and monopolar stimulation (24.9 ± 10.8 vs. 25.4 ± 9.0 months, P = 0.76). Incongruously, the mean TEED applied throughout the lifetime cycle was significantly higher in patients with bipolar compared with monopolar stimulation (584 ± 213 vs. 387 ± 121 Joule; P < 0.01). CONCLUSIONS: Battery lifetime in GPi DBS for dystonia is substantially shorter compared with that reported in DBS for Parkinson's disease, caused by a considerably higher voltage and greater pulse width and therefore a higher TEED applied during the battery lifetime cycle. The commonly used equation to calculate TEED, however, seems to be correct only for monopolar, but not bipolar stimulation.

Deep frontal and periventricular age related white matter changes but not basal ganglia and infratentorial hyperintensities are associated with falls: cross sectional results from the LADIS study.

BACKGROUND: Global age related white matter changes (ARWMC) are associated with progressive gait disturbances and falls, hypothesised to result from interruptions of cortico-subcortical circuits controlling balance, posture and locomotion. METHODS: The location of ARWMC in a large cohort of elderly non-disabled individuals with reported falls was analysed, using the cross sectional data of the Leukoaraiosis and Disability (LADIS) study. Detailed anatomical distributions of ARWMC assessed by MRI studies were analysed with respect to falls and balance performance. RESULTS: The severity of global ARWMC was significantly associated with a history of falls in the year prior to study inclusion (22.2% in the mild, 31.6% in the moderate and 37.3% in the severe ARWMC group according to the Fazekas scale; p = 0.002). Analysing the anatomical distribution of ARWMC, using the semiquantitative Scheltens scale, in multivariate analysis, periventricular (p = 0.006) and frontal deep (p = 0.033) ARWMC were independently associated with falls. Furthermore, logistic regression identified frontal deep (p = 0.003) ARWMC, but not basal ganglia and infratentorial hyperintensities, as significantly associated with balance disturbances. CONCLUSION: The association of frontal and periventricular ARWMC with falls supports the hypothesis that interruption of frontal subcortical motor circuits lead to balance disturbances and hence to an increased risk for falls in ARWMC.

Association of gait and balance disorders with age-related white matter changes: the LADIS study.

OBJECTIVE: In the Leukoaraiosis and Disability (LADIS) Study, 11 European centers are evaluating the role of age-related white matter changes (ARWMC) as an independent determinant of the transition to disability in the elderly (65 to 84 years). We aimed at determining the influence of ARWMC on different objective measures of gait and balance. METHODS: Six hundred thirty-nine nondisabled individuals were prospectively enrolled and are being followed-up for 3 years. Subjects are graded in three standardized categories of ARWMC (mild, moderate, and severe) according to central MRI reading. Quantitative tests of gait and balance include the Short Physical Performance Battery (SPPB; range: 0 [poor] to 12 [normal]), a timed 8-m walk, and a timed single leg stance test. RESULTS: In cross-sectional analysis, deficiencies in gait and balance performance were correlated with the severity of ARWMC (SPPB: 10.2 +/- 2.1 in the mild, 9.9 +/- 2.0 in the moderate, 8.9 +/- 2.6 in the severe group; p < 0.001). Walking speed correlated with the severity of ARWMC (1.24 +/- 0.28 m/second in the mild, 1.18 +/- 0.32 m/second in the moderate, and 1.09 +/- 0.31 m/second in the severe group; p < 0.001). Balance was best in individuals with mild ARWMC (single leg stance time: 18.9 +/- 10.8 seconds) compared with moderate and severe ARWMC (16.4 +/- 10.8 and 13.6 +/- 11.2 seconds) (p < 0.001). Physically inactive individuals had a higher risk of a pathologic SPPB score (moderate vs mild ARWMC: odds ratio 1.60, 95% CI 1.02 to 2.52; severe vs mild ARWMC: odds ratio 1.75, 95% CI 1.09 to 2.80). CONCLUSIONS: Our findings support a strong association between the severity of age-related white matter changes and the severity of gait and motor compromise. Physical activity might have the potential to reduce the risk of limitations in mobility.

Clinical significance of corpus callosum atrophy in a mixed elderly population.

Corpus callosum (CC) is the main tract connecting the hemispheres, but the clinical significance of CC atrophy is poorly understood. The aim of this work was to investigate clinical and functional correlates of CC atrophy in subjects with age-related white matter changes (ARWMC). In 569 elderly subjects with ARWMC from the Leukoaraiosis And DISability (LADIS) study, the CC was segmented on the normalised mid-sagittal magnetic resonance imaging (MRI) slice and subdivided into five regions. Correlations between the CC areas and subjective memory complaints, mini mental state examination (MMSE) score, history of depression, geriatric depression scale (GDS) score, subjective gait difficulty, history of falls, walking speed, and total score on the short physical performance battery (SPPB) were analyzed. Significant correlations between CC atrophy and MMSE, SPPB, and walking speed were identified, and the CC areas were smaller in subjects with subjective gait difficulty. The correlations remained significant after correction for ARWMC grade. In conclusion, CC atrophy was independently associated with impaired global cognitive and motor function in subjects with ARWMC.

Simple versus complex assessment of white matter hyperintensities in relation to physical performance and cognition: the LADIS study.

BACKGROUND: White matter hyperintensities (WMH) on MRI are associated with disorders of gait and balance and with cognitive impairment. The most suitable method to assess WMH in relation to the clinical evaluation of disturbances in these areas has not yet been established. AIM: To compare a simple visual rating scale, a detailed visual rating scale and volumetric assessment of WMH with respect to their associations with clinical measures of physical performance and cognition. METHODS: Data were drawn from the multicentre, multinational LADIS study. Data of 574 subjects were available. MRI analysis included assessment of WMH using the simple Fazekas scale, the more complex Scheltens scale and a semi-automated volumetric method. Disturbances of gait and balance and general cognitive function were assessed using the Short Physical Performance Battery (SPPB) and the Mini Mental State Examination (MMSE), respectively. RESULTS: Irrespective of the method of measuring WMH, subjects with disturbances of gait and balance (SPPB < or = 10) had more WMH than subjects with normal physical performance. Subjects with mild cognitive deficits (MMSE < or = 25) had more WMH than subjects with normal cognition. Correlations between clinical measures and WMH were equal across methods of WMH measurement (SPPB: Spearman r = -0.22, -0.25, -0.26, all p < 0.001; MMSE: Spearman r = -0.11, -0.10, -0.09, all p < 0.05, for Fazekas scale, Scheltens scale and volumetry, respectively). These associations remained significant and comparable after correcting for age, gender and education in multivariate linear regression analyses. CONCLUSION: Simple and complex measures of WMH yield comparable associations with measures of physical performance and cognition. This suggests that a simple visual rating scale may be sufficient, when analyzing relationships between clinical parameters and WMH in a clinical setting.

[Subcortical vascular encephalopathy]. / Subkortikale Vaskuläre Enzephalopathie.

Subcortical Vascular Encephalopathy (SVE) is an increasingly diagnosed disease with an enormous socio-economic impact. SVE leads to a progressive disability with immobilisation because of gait- and postural disturbances and with a progressive subcortical vascular dementia which is composed of cognitive slowing, loss of initiative and forgetfulness. A valid diagnosis has become possible only through a clear improvement in cerebral imaging techniques developed in the eighties. This explains, why so many different and confusing terms exist to describe the syndrome. The pathophysiological basis is a cerebral microangiopathy leading to lacunar infarcts and to diffuse ischemic white matter lesions, often occurring side by side. Taken together, such lesions lead to an interruption of parallel functional prefrontal-subcortical circuits, which are essential for psychomotor function. Neuroradiological methods like computed tomography (CT) and magnetic resonance imaging (MRI) are essential for the diagnosis. The prognosis is rather unfavourable. Several consensus meetings have established clinical and diagnostic criteria, which can serve as a basis for therapeutical trials. This review delineates diagnostic milestones, discusses etiological and pathophysiological mechanisms, and displays therapeutical options.

Alterations of cortical electrical activity in patients with sacral neuromodulator.

OBJECTIVES: Sacral neuromodulation represents chronic stimulation of the sacral (S3) nerve. So far, the mode of action and neuro-anatomical basis is unclear. Sacral reflex mechanisms as well as pontine or cortical centers of modulation have been postulated. Our aim was to evaluate possible alterations in electroencephalogram (EEG) activity as an indicator of a supraspinally mediated mechanism of sacral neuromodulation. MATERIALS AND METHODS: We analyzed serial EEGs (apparatus: Kölner Vitaport System) using electrodes placed at Fz, Cz, Cz' and Pz in 10 patients. Subsequently, the sacral (S3) nerve was stimulated by means of an impulse generator (Medtronic, Interstim 3023) using an on-off paradigm with a 1.5s "on" interval followed by a 10s stimulation break. Raw data were analyzed using both Matlab 4.0 software and a specially developed averaging routine. RESULTS: All patients demonstrated a cortical potential complex following sacral root stimulation with an early electronegative component at 50 ms with a mean amplitude of 23 microV followed by a late potential component with a mean latency of 253 ms and a mean amplitude of 5 microV, both with a maximum at Cz, corresponding to the post-central gyrus. This finding occurred irrespective of patient's reports of actually feeling the neuromodulator being switched on and off. CONCLUSION: In neuromodulation responders, both short and long latency cortical potentials can be reproduced with a maximum at the sensory cortical area. Although these potentials are similar to cognitively mediated "event-related potentials", they are clearly distinct from any subjective sensory or even painful response since several patients of this series have not been able to feel any neuromodulator action. Therefore, this pilot study indicates a supraspinally mediated site of modulation, most probably in sensory cortex areas.

Amantadine increases gait steadiness in frontal gait disorder due to subcortical vascular encephalopathy: a double-blind randomized placebo-controlled trial based on quantitative gait analysis.

In a randomized, double-blind placebo-controlled trial, 40 patients diagnosed as subcortical vascular encephalopathy (SVE) were given a daily dose of 500 ml i.v. amantadine vs. placebo for 5 days. Both groups were treated with physiotherapy on a daily basis. Quantitative gait analyses were performed at days 1 and 6 to evaluate gait steadiness from cadence, length of heel-to-toe movements, variability of centre of gravity (COG) and double support time. Both placebo- and amantadine-receiving patient groups showed mild improvement in gait parameters after study, which failed to show the superiority of amantadine, when comparing drug-induced changes between both groups. However, analysing the treatment effects from day 0 to day 6 in both groups separately, statistically significant changes could be found in the amantadine group for cadence, length of heel-to-toe movements in single support phase as well as for variability in double support phase and double support time (two-tailed paired t-test, p < 0.05), whereas in the placebo group, a statistically significant effect could only be seen for double support time (p < 0.05). In this small pilot study, amantadine tends to improve gait steadiness as evaluated by cadence, length of heel-to-toe movements in single support phase, variability in double support phase and double support time, in patients with moderate frontal gait disorder due to SVE. Improvements in the placebo group can be interpreted as physiotherapy effect, which improved gait steadiness slightly, however, this was statistically significant only for double support time.

Vasoneuronal coupling in migraineurs after subcutaneous sumatriptan: a TCD study.

According to the trigeminovascular model of pain in migraine, sterile neurogenic inflammation of dural vessels stimulates nociceptive fibres of the trigeminal nerve. Sumatriptan, a 5-HT1 receptor agonist, blocks this reaction and mediates vasoconstriction of meningeal arteries. However, it is uncertain, whether sumatriptan also has a vasoconstrictive effect on cerebral arteries, which may influence vasoneuronal coupling and induce secondary cerebral blood flow changes. We studied changes of cerebral blood flow velocity (CBFV) and the pulsatility index (PI) in the posterior cerebral artery (PCA) after stimulus activation before, 10 min and 30 min after subcutaneous application of 6 mg sumatriptan, in order to assess potential vasoactive effects on cerebral circulation. CBFV was recorded from both PCAs simultaneously in 27 migraineurs (twenty women, seven men, mean age 29 years), and arterial blood pressure (BP), heart rate (HR) and respiration rate (RR) were monitored. Although the mean diastolic blood pressure rose significantly from 75 mm Hg to 81 mm Hg (P<0.05) and systolic blood pressure and respiration rates remained constant, average CBFV values remained constant. Similarly, the relative increase of CBFV by visual stimulation, which is clearly higher compared to controls in other studies (55.0% before, 52.6% after 10 min, and 52.4% after 30 min), and absolute mean values for CBFV and PI did not change after visual stimulation. These results provide evidence against the hypothesis that sumatriptan produces vasoconstriction in the intracranial human arterial circulation as a potential risk of cerebral ischemia.