Clinical and Cognitive Features of Idiopathic Normal Pressure Hydrocephalus

Introduction: Idiopathic normal pressure hydrocephalus (iNPH) is characterized by dilated cerebral ventricles with progressive impaired gait, cognition, and urinary control. Firstly described in 1965 by Hakim and Adam, it remains largely under-diagnosed. The diagnosis is based on clinical and imaging (CT or MRI) investigations; a timely diagnosis and cerebrospinal fluid (CSF) shunt surgery has reported to be beneficial in 60 up to 80% of the cases

Pisa syndrome in Idiopathic Normal Pressure Hydrocephalus.

Abstract Introduction Idiopathic Normal Pressure Hydrocephalus (iNPH) is a complex syndrome of ventriculomegaly that can include parkinsonian-like features besides the classical triad of cognitive decline, urinary incontinence, and gait/balance disturbances. Pisa syndrome (PS) is a postural abnormality often associated with parkinsonism and defined as lateral trunk flexion greater than 10° while standing that resolves in the supine position. We reported a case series of classical "fixed" PS and one case of "Metronome" recurrent side-alternating PS in iNPH, displaying opposite electromyographic patterns of paraspinal muscles. Methods Eighty-five iNPH patients were followed longitudinally for at least one year through scheduled clinical and neuropsychological visits. Results Five (5.9%) subjects revealed PS. None of them had nigrostriatal dopaminergic involvement detected by [123I]FP-CIT SPECT. Among these patients, four had "fixed" PS, whereas one showed a recurrent side-alternating PS which repeatedly improved after ventriculo-peritoneal shunt and following adjustments of the valve-opening pressure of the shunt system. Discussion This is the first case series of PS in iNPH and the first report of "Metronome" PS in iNPH. The prompt response of the abnormal trunk postures through cerebrospinal fluid (CSF) shunt surgery suggests a causative role of an altered CSF dynamics. PS and gait disorders in iNPH could be explained by a direct involvement of cortico-subcortical pathways and subsequent secondary brainstem involvement, with also a possible direct functional damage of the basal ganglia at the postsynaptic level, due to enlargement of the ventricular system and impaired CSF dynamics. The early detection of these cases supports a proper surgical management

Phase matters: A role for the subthalamic network during gait.

The role of the subthalamic nucleus in human locomotion is unclear although relevant, given the troublesome management of gait disturbances with subthalamic deep brain stimulation in patients with Parkinson's disease. We investigated the subthalamic activity and inter-hemispheric connectivity during walking in eight freely-moving subjects with Parkinson's disease and bilateral deep brain stimulation. In particular, we compared the subthalamic power spectral densities and coherence, amplitude cross-correlation and phase locking value between resting state, upright standing, and steady forward walking. We observed a phase locking value drop in the β-frequency band (≈13-35Hz) during walking with respect to resting and standing. This modulation was not accompanied by specific changes in subthalamic power spectral densities, which was not related to gait phases or to striatal dopamine loss measured with [123I]N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)nortropane and single-photon computed tomography. We speculate that the subthalamic inter-hemispheric desynchronization in the β-frequency band reflects the information processing of each body side separately, which may support linear walking. This study also suggests that in some cases (i.e. gait) the brain signal, which could allow feedback-controlled stimulation, might derive from network activity

Striatal Dopaminergic Innervation Regulates Subthalamic Beta-Oscillations and Cortical-Subcortical Coupling during Movements: Preliminary Evidence in Subjects with Parkinson's Disease

Activation of the basal ganglia has been shown during the preparation and execution of movement. However, the functional interaction of cortical and subcortical brain areas during movement and the relative contribution of dopaminergic striatal innervation remains unclear. We recorded local field potential (LFP) activity from the subthalamic nucleus (STN) and high-density electroencephalography (EEG) signals in four patients with Parkinson’s disease (PD) off dopaminergic medication during a multi-joint motor task performed with their dominant and non-dominant hand. Recordings were performed by means of a fully-implantable deep brain stimulation (DBS) device at 4 months after surgery. Three patients also performed a single-photon computed tomography (SPECT) with [123I]N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)nortropane (FP-CIT) to assess striatal dopaminergic innervation. Unilateral movement execution led to event-related desynchronization (ERD) followed by a rebound after movement termination event-related synchronization (ERS) of oscillatory beta activity in the STN and primary sensorimotor cortex of both hemispheres. Dopamine deficiency directly influenced movement-related beta-modulation, with greater beta-suppression in the most dopamine-depleted hemisphere for both ipsi- and contralateral hand movements. Cortical-subcortical, but not interhemispheric subcortical coherencies were modulated by movement and influenced by striatal dopaminergic innervation, being stronger in the most dopamine-depleted hemisphere. The data are consistent with a role of dopamine in shielding subcortical structures from an excessive cortical entrapment and cross-hemispheric coupling, thus allowing fine-tuning of movement

Spectral profiles (single subject) during resting, upright standing and gait.

<p>Single subject spectral power of the STN local field potential during resting (blue line), standing (pink line) and gait for the two hemispheres, with less (–) and more (+) striatal dopamine innervation. Axial slices are left-right flipped to match the corresponding STN. The peak at 32 Hz is a known artefact of the Activa PC+S^® system tied to clock settings or due to a triggered check of the battery status. SPECT scans (central column) show striatal dopaminergic loss as percentage decline with respect to healthy subjects (calculated from BP_ND of DAT, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0198691#pone.0198691.t003" target="_blank">Table 3</a>).</p

Modulation of the spectral power during the gait cycle.

<p>Event related synchronization (ERS) and desynchronization (ERD) in low <i>β-</i> (top) high <i>β-</i> (middle) and <i>γ</i>-frequency band (bottom). Subthalamic power changes of the phases of gait are shown as the average relative change of the whole stride of all subjects. Shaded areas represent the confidence intervals (5–95%) of the group mean. We analyzed the power changes of STN–and STN+ during the gait cycle of the contralateral foot (but they could be also referred to the matched gait phases of the ipsilateral one). Stance is the period during which the foot is on the ground (dark and light orange bars). The stance phase includes a period of bilateral foot contact with the floor (double-support phases [dark orange bars]), and a period of unilateral foot contact (single-support phase [light orange bar]). The swing phase (light green and dark green bars) is the interval in which the foot is lifted from the floor. Thanks to the velocity peak (VP) of the marker placed on the lateral malleolus, we identified an acceleration (light green) a deceleration (dark green) sub-phase of the swing phase. HS = heel strike; TO = toe off; VP = velocity peak; lower case subscript indicates the foot contralateral _(contra) or ipsilateral _(ipsi) to STN–or STN+.</p

Inter-hemispheric coherence.

<p>Inter-hemispheric coherence (Coh, top panel), phase locking value (PLV, bottom left plot) and amplitude cross-correlation (CC, bottom right plot) during resting state (blue line), upright standing (pink line) and walking (green line). Statistical significance (red bar, paired Wilcoxon test, <i>p</i><0.05 uncorrected) was reached for the PLV selectively in the <i>β</i>-frequency band between resting state and walking. Shaded areas represent the confidence intervals (5–95%) of the group mean.</p

Anthropometric and kinematic data.

<p>Anthropometric and kinematic data.</p

Non-displaceable binding potentials of dopamine reuptake transporters.

<p>Non-displaceable binding potentials of dopamine reuptake transporters.</p

Spectral profiles (average) during resting, upright standing, and gait.

<p>Average spectral power of the STN local field potential during resting (blue line), standing (pink line) and gait (green line) for the two hemispheres, with less (–) and more (+) striatal dopamine innervation. Results are corrected for the nominal noise floor level of the device (150nV/rtHz, [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0198691#pone.0198691.ref032" target="_blank">32</a>,<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0198691#pone.0198691.ref033" target="_blank">33</a>]), all values above 0dB/Hz are reliable. Shaded areas represent the confidence intervals (5–95%) of the group mean. The peak at 32 Hz is a known artefact of the Activa PC+S^® system tied to clock settings or due to a triggered check of the battery status.</p