Quantifying Brain Iron in Hereditary Hemochromatosis Using R2* and Susceptibility Mapping.

BACKGROUND AND PURPOSE: Brain iron dyshomeostasis is increasingly recognized as an important contributor to neurodegeneration. Hereditary hemochromatosis is the most commonly inherited disorder of systemic iron overload. Although there is an increasing interest in excessive brain iron deposition, there is a paucity of evidence showing changes in brain iron exceeding that in healthy controls. Quantitative susceptibility mapping and R2* mapping are established MR imaging techniques that we used to noninvasively quantify brain iron in subjects with hereditary hemochromatosis. MATERIALS AND METHODS: Fifty-two patients with hereditary hemochromatosis and 47 age- and sex-matched healthy controls were imaged using a multiecho gradient-echo sequence at 3T. Quantitative susceptibility mapping and R2* data were generated, and regions within the deep gray matter were manually segmented. Mean susceptibility and R2* relaxation rates were calculated for each region, and iron content was compared between the groups. RESULTS: We noted elevated iron levels in patients with hereditary hemochromatosis compared with healthy controls using both R2* and QSM methods in the caudate nucleus, putamen, pulvinar thalamus, red nucleus, and dentate nucleus. Additionally, the substantia nigra showed increased susceptibility while the thalamus showed an increased R2* relaxation rate compared with healthy controls, respectively. CONCLUSIONS: Both quantitative susceptibility mapping and R2* showed abnormal levels of brain iron in subjects with hereditary hemochromatosis compared with controls. Quantitative susceptibility mapping and R2* can be acquired in a single MR imaging sequence and are complementary in quantifying deep gray matter iron.

Medication status and dual-tasking on turning strategies in Parkinson disease.

BACKGROUND: Parkinson disease (PD) patients have turning impairments that may increase fall risk. Clinics lack specialized kinematic equipment used in gait and turn analysis and require a simple method to evaluate fall risk and advise patients in turning strategy selection. OBJECTIVES: To enhance understanding of PD turning strategies and determine if turning can be assessed using a video-recording and categorization method, we compared 180-degree and 90-degree turns as a function of medication status and dual-tasking (DT). METHODS: 21 PD participants (H&Y stage 1-3) in PD-ON and PD-OFF medication states and 16 controls completed 180-degree and 90-degree turn-tasks with and without DT. Video-recordings of tasks permitted classification of 180-degree turns into Few-Step turns (FST) vs. Multi-Step turns (MST) and 90-degree turns into Step vs. Spin-turns. FST were further sub-classified into Twisting vs. Sideways turns and MST into Backward, Festination, Forward or Wheeling turns. Percentages of subtypes were analyzed across groups by task. RESULTS: IN 180-degree tasks, there was an effect of group: FST vs. MST F(2,55) = 9.578, p < .001. PD participants in the off-medication state (PD-OFF) produced significantly more MST with a larger number of different turning subtypes vs. controls or PD on medication (PD-ON). In 90-degree tasks, controls significantly increased their proportion of Step-turns while DT (p < .001), an adaptation not observed in PD-ON or PD-OFF. CONCLUSIONS: PD turning impairments may stem from an inability to select a unified turning strategy and to adapt to the turning environment, which may be exacerbated in PD-OFF. Video-analysis may prove beneficial in predicting a clinical course for PD patients by revealing features of turning dysfunction.

An evaluation of sensorimotor integration during locomotion toward a target in Parkinson's disease.

Recent research suggests that basal ganglia dysfunction may result in problems integrating concurrent vision and proprioception during movement. We evaluated dopaminergic system involvement in this sensorimotor process during locomotion within a large sample of Parkinson's disease (PD) patients while "On" and "Off" their dopaminergic medications (n=25), in conditions that selectively manipulated the availability of proprioception, vision or both. The present experiment focused on two main objectives: i) to examine the relative influence of visual and proprioceptive inputs on locomotion and target accuracy in patients with PD; and ii) to examine the influence of dopamine replacement therapy on sensorimotor integration while moving toward the target. All participants walked at a self-selected pace on a GAITRite carpet in two baseline conditions (light and dark), as well as four experimental darkness conditions: a) to a remembered target (i.e. proprioception only), b) to a remembered target with light on chest for body position awareness (proprioception plus), c) with vision of a lit target, also with light on chest (vision and proprioception), d) pushed in wheelchair to remembered target (no proprioception or vision). Final position was measured by 2-D radial error, and revealed a group by condition interaction, suggesting that PD patients "Off" their medications move to targets with less accuracy, but approach the accuracy of healthy participants when in the "On" state. Both PD and healthy improved their accuracy with availability of concurrent vision and proprioception (condition c). Interestingly, our results demonstrate that PD "Off" performed the task with greater difficulty than when "On" medication, but only when proprioception was the sole source of feedback. Since PD, whether medicated or unmedicated were even more affected when proprioception was removed (wheelchair), a memory-related explanation can be ruled out. Our results suggest that the basal ganglia are not specifically involved in visuoproprioceptive integration; however, assimilation of proprioceptive feedback to guide an ongoing movement may be a critical function of the basal ganglia.

Tetrode technology: advances in implantable hardware, neuroimaging, and data analysis techniques.

The technical advances in hardware and software for multiunit recordings have made it easier to gather data from a large number of neurons for behavioral correlations. This paper discusses several such advances in implantable hardware, magnetic resonance imaging of electrodes in situ, and data analysis software for multiple simultaneous signals.

Methods for digital video recording, storage, and communication of movement disorders.

Video technology has now reached a level of sophistication that allows easy digitization. Digital video can be easily edited, reproduced, incorporated into databases, and posted on intra- and Internet sites for clinical use and demonstration purposes. Numerous methods exist for the production of digital video. This article synthesizes and simplifies the available methodologies in order to easily choose the technology that is the most appropriate for the movement disorder specialist's end use. Depending on available resources, issues such as cost, ease, and time to conversion are discussed. In addition, our experience with the use of one of the methodologies is briefly presented.

A dynamical-systems model for Parkinson's disease.

The juxtaposition of hypokinetic and hyperkinetic symptoms in Parkinson's disease (PD) presents a challenge in modeling the basal ganglia. We propose a model of the striatum that can account for the mixture of symptoms seen in PD. In the model, the problem of motor planning is cast in terms of a particle in a potential, where potentials are generated internally in striatal modules, subject to afferent control. Planned movement is governed by Hamilton's equations, where potential energy is supplied by potentials expressed in the striatum. To test the model in realistic situations, a dynamic simulation of a two-link robot arm was used. Normal movement is modeled and shown to exhibit observed experimental properties. Symptoms of PD are reproduced by modeling hypothetical consequences of PD pathology.

Building neural representations of habits.

Memories for habits and skills ("implicit or procedural memory") and memories for facts ("explicit or episodic memory") are built up in different brain systems and are vulnerable to different neurodegenerative disorders in humans. So that the striatum-based mechanisms underlying habit formation could be studied, chronic recordings from ensembles of striatal neurons were made with multiple tetrodes as rats learned a T-maze procedural task. Large and widely distributed changes in the neuronal activity patterns occurred in the sensorimotor striatum during behavioral acquisition, culminating in task-related activity emphasizing the beginning and end of the automatized procedure. The new ensemble patterns remained stable during weeks of subsequent performance of the same task. These results suggest that the encoding of action in the sensorimotor striatum undergoes dynamic reorganization as habit learning proceeds.

Chronic acquired hepatocerebral degeneration: case reports and new insights.

Chronic acquired hepatocerebral degeneration (CAHD) is a heterogeneous disorder that can occur with a primary neurologic, hepatic, or combined presentation. Little has been added to the understanding of this disorder since the detailed, early clinical and pathological descriptions. The spectrum of clinical presentations can be neuropsychiatric (apathy, lethargy, excessive somnolence), a movement disorder (ataxia, tremor, chorea, parkinsonism, myoclonus, dystonia), or both. Cortical laminar necrosis and polymicrocavitation in the cortex and basal ganglia are combined with cerebral and cerebellar atrophy. Microscopically, Alzheimer type II astrocytes and cytoplasmic glycogen granules are characteristic. Recent neuroradiological observations in patients with liver failure have shown a specific magnetic resonance (MR) imaging appearance with a hyperintense T1 signal in the pallidum, putamen, and, rarely, mesencephalon. Using clues from a similar MR appearance in patients receiving total parenteral nutrition as well as animals given parenteral manganese, and the knowledge that manganese is cleared by the hepatobiliary system, deposition of manganese in the brain is postulated in patients with CAHD. In this review we describe three cases of CAHD with detailed clinical and radiological documentation and discuss the aforementioned pathogenetic mechanisms.

Femoral neuropathy in renal transplantation.

Acute femoral neuropathy after renal transplantation is an uncommon and rarely recognized complication. Recovery of the nerve is usual. Although rare, five cases have come to our attention in the past twenty years. A detailed clinical and electrophysiological analysis with a six month follow-up is presented. A review of sixteen other reported cases is also provided. The possible pathophysiology including direct compression and nerve ischemia, is discussed. We believe that nerve ischemia, possibly caused by a steal phenomenon, occurs in all cases following the anastomosis of the graft renal artery to the internal iliac artery, with a superimposed component of compression in some cases. The severity of ischemia probably determines the degree of recovery.

Stiff-person syndrome.

The stiff-person syndrome is a disorder of persistent, painful muscle contractions predominately affecting the axial musculature. We describe a patient with this disorder and review its pathophysiology. Molecular biologic and immunologic techniques have recently added to the understanding of the mechanism of this disorder. Association with diseases such as diabetes, vitiligo and hypothyroidism have strengthened the auto-immune nature of this syndrome. Auto-antibodies against glutamic acid decarboxylase (GAD), an intraneuronal enzyme, have been implicated in the etiology of this unique disease. Therapeutic intervention with agents such as benzodiazepines that modify central GABAergic activity have demonstrated significant benefit in patients with stiff-person syndrome.