[Rehabilitation possibilities and results after neurosurgical intervention of brain tumors]. / Az agydaganat mutéti kezelését követo rehabilitáció lehetosége, eredményei.

BACKGROUND AND PURPOSE: Authors examined the rehabilitation possi-bi-lities, necessities, and results of patients after operation with brain tumor, and report their experiences. METHODS: Retrospective, descriptive study at the Brain Injury Rehabilitation Unit, in National Institute for Medical Rehabilitation. Patients were admitted consecutively after rehabilitation consultation, from different hospitals, following surgical intervention of brain tumors, between 01 January 2001 and 31 December 2016. Patients participated in a postacute inpatient rehabilitation program, in multidisciplinary team-work, leaded by Physical and Rehabilitation Medicine specialist included the following activities: rehabilitation nursing, physical, occupational, speech, psychological and neuropsychological therapy. RESULTS: At the rehabilitation unit, in the sixteen-year period 84 patients were treated after operation with brain tumor. Patients arrived at the unit after an average of 41 days to the time of the surgical intervention (range: 10-139 days), and the mean length of rehabilitation stay was 49 days (range: 2-193 days). The mean age of patients was 58 years (20-91), who were 34 men and 50 women. The main symptoms were hemiparesis (64), cognitive problems (26), dysphagia (23), aphasia (16), ataxia (15), tetraparesis (5), and paraparesis (1). The mean Barthel Index at the time of admission was 35 points, whereas this value was 75 points at discharge. After the inpatient rehabilitation, 73 patients improved functionally, the status of 9 patients did not show clinically relevant changes, and 2 patients deteriorated. During the rehabilitation 10 patients required urgent interhospital transfer to brain surgery units, 9 patients continued their oncological treatment, two patients continued rehabilitation treatment at another rehabilitation unit, and after rehabilitation 73 patients were discharged to their homes. CONCLUSION: Inpatient rehabilitation treatment could be necessary after operation of patients with brain tumor especially when functional disorders (disability) are present. Consultation is obligatory among the neurosurgeon, rehabilitation physician and the patient to set realistic rehabilitation goals and determine place and method of rehabilitation treatment, but even at malignancies cooperation with oncological specialist also needed. Authors' experience shows benefits of multidisciplinary rehabilitation for patients after brain tumor surgery.

Insights into the structure and function of the hippocampal formation: Relevance to Parkinson's disease.

The link between the hippocampus and declarative memory dysfunctions following the removal of the medial temporal lobe opened unexplored fields in neuroscience. In the first part of our review, we summarized current theoretical frameworks discussing the role of hippocampus in learning and memory. Several theories are highlighted suggesting that the hippocampus is responsible for assembling stimulus elements into a unitary representation that later can be utilized to simulate future events. The hippocampal formation has been implicated in a growing number of disorders, from neurodegenerative diseases to atypical cognitive ageing and depression. Recent neuroimaging studies provided new opportunities to study in detail the hippocampal formation's role in higher levels of the nervous system. We will present data regarding the regional specialization of the hippocampus in experimental models developed for healthy and neurological conditions with a special focus on Parkinson's disease. Combined evidence from neuroimaging studies suggested that hippocampal volume is reduced in non-demented, newly diagnosed patients with Parkinson's disease, which is associated with impaired memory performance. These findings proposed that, beyond the well-known striatal dopamine loss, impaired hippocampal synaptic plasticity may contribute to cognitive and affective impairments in early Parkinson's disease.

A single dose of L-DOPA changes perceptual experiences and decreases latent inhibition in Parkinson's disease.

Despite the well-known neuropsychiatric side effects of dopaminergic medications, the possible subjective psychotomimetic effects of a single dose of L-DOPA in newly diagnosed, drug-naïve patients with Parkinson's disease (PD) are not known. To investigate this question, we used a visual search task for latent inhibition (LI), the Community Assessment of Psychic Experiences (CAPE) scale, and visual analog scales for psychotomimetic effects (perception, relaxation, and dysphoria) in 28 de novo PD patients before (off) and after (on) the adminstration of L-DOPA and in 25 matched healthy control individuals. Results revealed increased LI in PD-off and decreased LI in PD-on relative to the control subjects. After the administration of L-DOPA, we observed a significant decline in LI in PD. L-DOPA also enhanced perceptual experiences (changes in subjective feelings in thinking, time perception, and mental "highness"). Greater reduction in LI was associated with enhanced perceptual experiences. These results suggest that a single dose of L-DOPA has a significant psychotomimetic effect, which is associated with decreased LI, a behavioral marker of psychosis-like experiences.

Behavioural aspects of a modified crosstalk between basal ganglia and limbic system in Parkinson's disease.

Dysfunctions in dopaminergic neurotransmission lead to motor symptoms and cognitive impairments associated with behavioural disturbances. Parkinson's disease is a neurodegenerative disorder which is primarily characterized by an abnormal basal ganglia activity. Recently, increased attention has been directed towards the hippocampus in the development of non-motor symptoms. Given the temporal progression of the disease, dopaminergic depletion firstly affects the dorsal striatum leaving the ventral striatum relatively intact. However, it is possible that the structure and function of the hippocampus shows alterations even in early stages of Parkinson's disease. Subtle cognitive impairments occur in the earliest stages, and therefore Parkinson's disease could provide a unique model to investigate the effect of replacement therapies on a neural network with different baseline dopaminergic levels. Strong evidence suggests that dopaminergic medications improve the motor symptoms, but these medications might have disadvantageous effects on cognitive functions. In this review, we examine the role of dopaminergic changes across several cognitive and behavioural impairments observed in Parkinson's disease, with a special reference to hippocampal dysfunctions.

[Application of levodopa/carbidopa intestinal gel in advanced Parkinson's disease]. / Levodopa/carbidopa intesztinális gél alkalmazása elorehaladott Parkinson-kórban.

Parkinson's disease is the second most common neurodegenerative disorder around the world. Levodopa has remained the "gold standard" of the therapy even several decades after its introduction. Chronic levodopa treatment is associated with the development of motor complications in most patients. Advanced Parkinson's disease is characterized by these complications: motor and non-motor fluctuation and disturbing dyskinesia. Continuous dopaminergic stimulation might reduce these complications. In advanced Parkinson's disease levodopa is still effective. In the treatment of this stage there are several advanced or device-aided therapies: apomorphine pump, deep brain stimulation and levodopa/carbidopa intestinal gel. Levodopa/carbidopa intestinal gel is an aqueous gel that can be delivered to the jejunum via a percutaneous gastrojejunostomy tube which is connected to an infusion pump dosing the levodopa gel continuously to the place of absorption. Levodopa/carbidopa gel infusion can be used as monotherapy, can be tested, can be used individually and this therapy is reversible. Several clinical trials demonstrated that levodopa/carbidopa intestinal gel therapy is of long-term benefit, improves the quality of life of the patients and can reduce motor fluctuation and dyskinesia.

[Bronchoscopy-guided decannulation of tracheostomy in patients with brain injury]. / Agysérült betegek tracheostomájának dekanülálása bronchoszkópos ellenorzés mellett.

INTRODUCTION: Progress in intensive care management of patients with severe brain injury due to trauma or vascular lesion significantly improved the mortality and increased the number of patients with tracheostomy who undergo treatment in rehabilitation departments. AIM: The aim of the authors was to describe the safe tracheostomy decannulation method of patients with brain injury during rehabilitation. METHOD: A prospective, descriptive study performed at the rehabilitation departments of the National Institute for Medical Rehabilitation in Budapest, Hungary. RESULTS: From January 1 until December 31, 2013, thirty examinations with flexible bronchoscope for tracheostomy decannulation were performed in 20 patients. The patients were admitted to the rehabilitation wards with various brain injuries: 6 patients suffered from trauma, 5 had ischemic stroke, 3 patients had brain stem haemorrhage, 2 patients cerebellar and one patient bifrontal haemorrhage. One patient had menangioma, and one had multiple organ failure and anoxic brain injury caused by pneumonia. The average age of patients was 44 years (range, 18-80 years). During the procedure successful decannulation was performed in 13 patients. Decannulation occurred 62 days after tracheostomy on average. CONCLUSIONS: Safe patient care requires that various medical departments keep pace with the development of different specialities. To ensure early rehabilitation of patients with severe brain injury having tracheostomy, safe treatment and, if possible, decannulation should be performed. This procedure requires the involvement of a physician with bronchoscopy skills as well as the development of local protocols.

[Experience with levodopa/carbidopa intestinal gel in the treatment of advanced Parkinson's disease in Hungary]. / A levodopa/carbidopa intestinalis gél kezelés magyarországi tapasztalatai elorehaladott Parkinson-kórban.

In the advanced Parkison's disease (PD) the late complications of levodopa therapy have to be considered: motor and/or non-motor fluctuations with or without disturbing dyskinesias. The non-motor fluctuations often influence the quality of life (QoL) in a much more negative way compared with the motor symptoms. In the treatment of advanced PD there are several device-aided methods - deep brain stimulation, apomorphine pump, levodopa/carbidopa intestinal gel (LCIG) - to improve the symptoms, the QoL, sometimes even in an individual, tailored custom form. The LCIG therapy was introduced in Hungary in 2011. Here we summarize the data of our patients: we have tested almost 60 patients and in 43 cases we have started this treatment. We analyze the duration of illness, levodopa therapy, motor and non-motor fluctuation of patients and present our experiences with the test phase and the chronic LCIG therapy via PEG/PEJ implantation. We paid attention to the surgery and device - depending side effects. Our experiences are similar to the international data. In patients selection ,,the right treatment, to the right patient, in the right time" is of importance.

How attentional boost interacts with reward: the effect of dopaminergic medications in Parkinson's disease.

There is widespread evidence that dopamine is implicated in the regulation of reward and salience. However, it is less known how these processes interact with attention and recognition memory. To explore this question, we used the attentional boost test in patients with Parkinson's disease (PD) before and after the administration of dopaminergic medications. Participants performed a visual letter detection task (remembering rewarded target letters and ignoring distractor letters) while also viewing a series of photos of natural and urban scenes in the background of the letters. The aim of the game was to retrieve the target letter after each trial and to win as much virtual money as possible. The recognition of background scenes was not rewarded. We enrolled 26 drug-naïve, newly diagnosed patients with PD and 25 healthy controls who were evaluated at baseline and follow-up. Patients with PD received dopamine agonists (pramipexole, ropinirole, rotigotine) during the 12-week follow-up period. At baseline, we found intact attentional boost in patients with PD: they were able to recognize target-associated scenes similarly to controls. At follow-up, patients with PD outperformed controls for both target- and distractor-associated scenes, but not when scenes were presented without letters. The alerting, orienting and executive components of attention were intact in PD. Enhanced attentional boost was replicated in a smaller group of patients with PD (n = 15) receiving l-3,4-dihydroxyphenylalanine (L-DOPA). These results suggest that dopaminergic medications facilitate attentional boost for background information regardless of whether the central task (letter detection) is rewarded or not.

Delay discounting of reward and caudate nucleus volume in individuals with α-synuclein gene duplication before and after the development of Parkinson's disease.

BACKGROUND/AIMS: α-Synuclein (SNCA) may be a key factor in dopaminergic neurotransmission, reward processing, and neurodegeneration in Parkinson's disease (PD). We investigated delay discounting of reward and caudate volume in SNCA gene duplication carriers before and after the development of PD. METHODS: Participants were 7 presymptomatic SNCA duplication carriers who later developed PD (follow-up period: 5.4 years) and 10 matched non-carrier controls. At the follow-up assessment, patients received levodopa (L-DOPA) therapy. Delay discounting of reward was assessed with the Kirby discounting questionnaire. We measured the volume of the caudate nucleus and cerebral cortex using structural MRI and FreeSurfer software. RESULTS: In the presymptomatic stage, carriers showed similar delay discounting and caudate volume to that of non-carrier controls. However, after the development of PD, we observed a significant elevation in delay discounting (impulsive decisions) and reduced caudate volume. There was no cortical atrophy. CONCLUSION: Impaired reward-related decision making and caudate volume loss are not detectable in the presymptomatic stage in SNCA duplication carriers. These behavioral and neuroanatomical alterations are observed after the development of clinical symptoms when there is extensive neurodegeneration. Study limitations include a small sample size as well as the potential confounding effect of general cognitive decline.

[Treatment possibilities in advanced Parkinson's disease]. / Kezelési lehetoségek a Parkinson-kór elorehaladott stádiumában.

In the course of Parkinson's disease, advanced and late stages can be distinguished. In the advanced stage, levodopa has good effect on motor symptoms, but patient care is often hindered by levodopa-induced complications such as motor fluctuation and dyskinesias. In the late stage levodopa response becomes poor, falls, dementia and psychotic symptoms appear and patients often need hospitalization. In the advanced stage, the quality of life may be improved better by device-aided therapy than by best oral medical treatment. The alternatives are apomorhin pump, levodopa carbidopa intestinal gel with pump and deep brain stimulation. The therapy plan should be based on the principle: "the right treatment, to the right patient, at the right time".

Can somatosensory evoked potentials predict disease course in early multiple sclerosis patients?

BACKGROUND: Multiple sclerosis (MS) is an autoimmune degenerating disease, where myelin degradation as well as axonal loss is present. PURPOSE: To asses whether recording the middle-latency components of the median nerve somatosensory evoked potentials (SEPs) increases the diagnostic sensitivity in patients with MS, and to investigate whether any of the abnormalities correlates with the severity of the clinical signs and predicts future outcome. METHODS: Twenty consecutive MS patients at early onset were included. Median and tibial nerve SEPs were recorded at the time of the referral. Extended Disability Status Scale (EDSS) and Multiple Sclerosis Severity Score (MSSS) were assessed at the time of the referral and after 5-year followup. RESULTS: Recording the middle-latency components increased the sensitivity of the median nerve SEPs from 50% to 75%. The overall sensitivity of the SEPs (i.e. including also tibial nerve SEPs) modestly increased (from 80% to 90%). The amplitude of the cortical N20 potential of the median nerve was inversely correlated to the clinical severity. None of the parameters could predict the future outcome. CONCLUSIONS: Our results provide neurophysiological evidence for the role of axonal lesions in the clinical disability of the patients with MS.

Reward-learning and the novelty-seeking personality: a between- and within-subjects study of the effects of dopamine agonists on young Parkinson's patients.

Parkinson's disease is characterized by the degeneration of dopaminergic pathways projecting to the striatum. These pathways are implicated in reward prediction. In this study, we investigated reward and punishment processing in young, never-medicated Parkinson's disease patients, recently medicated patients receiving the dopamine receptor agonists pramipexole and ropinirole and healthy controls. The never-medicated patients were also re-evaluated after 12 weeks of treatment with dopamine agonists. Reward and punishment processing was assessed by a feedback-based probabilistic classification task. Personality characteristics were measured by the temperament and character inventory. Results revealed that never-medicated patients with Parkinson's disease showed selective deficits on reward processing and novelty seeking, which were remediated by dopamine agonists. These medications disrupted punishment processing. In addition, dopamine agonists increased the correlation between reward processing and novelty seeking, whereas these drugs decreased the correlation between punishment processing and harm avoidance. Our finding that dopamine agonist administration in young patients with Parkinson's disease resulted in increased novelty seeking, enhanced reward processing, and decreased punishment processing may shed light on the cognitive and personality bases of the impulse control disorders, which arise as side-effects of dopamine agonist therapy in some Parkinson's disease patients.

Cognitive sequence learning in Parkinson's disease and amnestic mild cognitive impairment: Dissociation between sequential and non-sequential learning of associations.

Evidence suggests that dopaminergic mechanisms in the basal ganglia (BG) are important in the learning of sequential associations. To test the specificity of this hypothesis, we assessed never-medicated patients with Parkinson's disease (PD) and amnestic mild cognitive impairment (aMCI) using a chaining task. In the training phase of the chaining task, each link in a sequence of stimuli leading to reward is trained step-by-step using feedback after each decision, until the complete sequence is learned. In the probe phase of the chaining task, the context of stimulus-response associations must be used (the position of the associations in the sequence). Results revealed that patients with PD showed impaired learning during the training phase of the chaining task, but their performance was spared in the probe phase. In contrast, patients with aMCI with prominent medial temporal lobe (MTL) dysfunctions showed intact learning during the training phase of the chaining task, but their performance was impaired in the probe phase of the chaining task. These results indicate that when dopaminergic mechanisms in the BG are dysfunctional, series of stimulus-response associations are less efficiently acquired, but their sequential manner is maintained. In contrast, MTL dysfunctions may result in a non-sequential learning of associations, which may indicate a loss of contextual information.

Possible role of the basal ganglia in the generation of the N30 potential of the median nerve somatosensory evoked potentials.

BACKGROUND AND PURPOSE: The origin and afferentation of the frontal N30 component of the median nerve somatosensory evoked potentials (SEPs) have not yet been fully elucidated. The aim of this study was to assess the possible selective impairment of the N30 component in patients with lacunar infarcts of the basal ganglia as compared to patients with lacunar infarctions sparing the basal ganglia and to a group of healthy subjects. METHODS: Median nerve SEPs were measured in ten patients with lacunar infarctions of the brain (but no cortical atrophy or leukoaraiosis) and 13 healthy volunteers. Four patients had lacunar infarctions affecting the basal ganglia and 6 patients had lesions affecting other structures. RESULTS: In two patients with lesions affecting the head of the caudate nucleus, there was no identifiable N30 component on the affected side. In one patient with bilateral lesions of the globus pallidus, the amplitude of the N30 component was significantly reduced. In one patient with lesion of the tail of the caudate nucleus, the N30 component was unaffected. The amplitude of the N30 component was also reduced in two patients with frontal subcortical white matter lesions. In all the other subjects, we recorded normal N30 components on both sides. CONCLUSION: Our results further support the importance of the basal ganglia, especially the head of the caudate nucleus in the generation of the N30 component of the median nerve SEPs.

Reduced CA2-CA3 Hippocampal Subfield Volume Is Related to Depression and Normalized by l-DOPA in Newly Diagnosed Parkinson's Disease.

Hippocampal dysfunctions may play an important role in the non-motor aspects of Parkinson's disease (PD), including depressive and cognitive symptoms. Fine structural alterations of the hippocampus and their relationship with symptoms and medication effects are unknown in newly diagnosed PD. We measured the volume of hippocampal subfields in 35 drug-naïve, newly diagnosed PD patients without cognitive impairment and 30 matched healthy control individuals. Assessments were performed when the patients did not receive medications and after a 24-week period of l-DOPA treatment. We obtained a T1-weighted 3D magnetization-prepared rapid acquisition gradient echo image at each assessment. FreeSurfer v6.0 was used for image analysis. Results revealed a selectively decreased CA2-CA3 volume in non-medicated PD patients, which was normalized after the 24-week treatment period. Higher depressive symptoms were associated with smaller CA2-CA3 volumes. These results indicate that the CA2-CA3 subfield is structurally affected in the earliest stage of PD in the absence of cognitive impairment. This structural anomaly, normalized by l-DOPA, is related to depressive non-motor symptoms.

Levodopa/carbidopa intestinal gel can improve both motor and non-motor experiences of daily living in Parkinson's disease: An open-label study.

BACKGROUND: Levodopa/carbidopa intestinal gel therapy (LCIG) can efficiently improve several motor and non-motor symptoms of advanced Parkinson's disease (PD). The recently developed Movement Disorder Society-sponsored Unified Parkinson's Disease Rating Scale (MDS-UPDRS) improved the original UPDRS making it a more robust tool to evaluate therapeutic changes. However, previous studies have not used the MDS-UPDRS and the Unified Dyskinesia Rating Scale (UDysRS) to assess the efficacy of LCIG. OBJECTIVES: Our aim was to determine if the MDS-UPDRS and UDysRS could detect improvement in the experiences of daily living following 1-year LCIG treatment. METHODS: In this prospective, multicenter, open-label study, 34 consecutive patients undergoing LCIG treatment were enrolled. Patients were examined twice: prior to LCIG initiation and 12 months later. Impact of PD-related symptoms and dyskinesia was assessed by the MDS-UPDRS and UDysRS. RESULTS: Non-motor Experiences of Daily Living part of MDS-UPDRS improved from 20 (median, interquartile-range, IQR:14-23) to 16 points (median, IQR:12-20, p = 0.044) and the Motor Experiences of Daily Living ameliorated from 24 (median, IQR:20-29) to 18 points (median, IQR:13-25, p = 0.025). Health-related quality of life, measured by PDQ-39, also improved from 35.4 (median, IQR:26.9-50.3) to 27.0 (median, IQR:21.3-31.4) points (p = 0.003). The total score of UDysRS decreased from 47 (median, IQR:36-54) to 34 (median, IQR:21-45) points (p = 0.003). CONCLUSIONS: As far as the authors are aware of, our paper is the first to evaluate the impact of LCIG on dyskinesia by the means of UDysRS. Changes in MDS-UPDRS and UDysRS confirm that LCIG treatment can efficiently improve experiences of daily living in advanced PD.

Dopamine improves exploration after expectancy violations and induces psychotic-like experiences in patients with Parkinson's disease.

Dopamine neurons are sensitive to novel and rewarding events, and dopamine signals can modulate learning in higher-level brain networks. Additionally, dopamine abnormalities appear to be central to the pathophysiology of schizophrenia spectrum disorders. In this study, we investigate the dopaminergic modulation of schizotypal traits and exploration after expectancy violations in Parkinson's disease (PD) patients on dopamine replacement therapy. Exploration after expectancy violations was measured with a latent inhibition and an anomaly categorisation task. Patients with PD had significantly elevated levels of schizotypy and reduced latent inhibition, relative to the controls. Anomaly categorisation was enhanced at trend level among the patients. Dopaminergic antiparkinsonian drugs showed dose-dependent effects: they induced psychotic-like experiences, and at the same time, they disrupted latent inhibition and made categorisation of anomaly more efficient. Most of these findings were replicated in an independent sample of patients with PD. An up-regulated dopamine system in medicated PD patients might tune higher-level brain networks to engage in learning when faced with unexpected information, and therefore hasten the updating of internal models.

The effect of sleep deprivation on median nerve somatosensory evoked potentials.

The purpose of the study was to determine the effect of one night's sleep deprivation on the early and middle-latency median nerve (MN) somatosensory evoked potentials (SEPs). In 20 healthy volunteers, SEPs in response to electrical stimulation of the MN at the wrist were recorded for the 100-ms post-stimulus period, before and after one night of sleep deprivation. The P14 latency was significantly prolonged after sleep deprivation. We found significant increases in the amplitudes of the early parietal (N20-P24) and the frontal middle-latency (P45-N60) components following sleep deprivation. Our results indicate that somatosensory processing is altered after sleep deprivation.

Somatosensory evoked potentials correlate with genetics in Huntington's disease.

Abnormalities of somatosensory evoked potentials (SEPs) have been reported in Huntington's disease, a neuropsychiatric disorder caused by the expansion of a CAG trinucleotide repeat. The aim of our study was to determine the relationship between these electrophysiological changes and the length of the nucleotide repeat. We found a striking correlation between the decrease in the early component amplitudes (N20 and N30) of the median nerve SEP and the repeat length, suggesting that these SEP alterations are indeed related to the genetically determined pathological process. The cortical components of the tibial nerve SEP exhibited a dramatic alteration in the patient group and were the only SEP changes found in the group of asymptomatic carriers of the mutation, being more sensitive than the median nerve SEPs.

The effect of dopamine agonists on adaptive and aberrant salience in Parkinson's disease.

Clinical evidence suggests that after initiation of dopaminergic medications some patients with Parkinson's disease (PD) develop psychotic symptoms, such as hallucinations and delusions. Here, we tested the hypothesis that the neurocognitive basis of this phenomenon can be defined as the formation of arbitrary and illusory associations between conditioned stimuli and reward signals, called aberrant salience. Young, never-medicated PD patients and matched controls were assessed on a speeded reaction time task in which the probe stimulus was preceded by conditioned stimuli that could signal monetary reward by color or shape. The patients and controls were re-evaluated after 12 weeks during which the patients received a dopamine agonist (pramipexole or ropinirole). Results indicated that dopamine agonists increased both adaptive and aberrant salience in PD patients, that is, formation of real and illusory associations between conditioned stimuli and reward, respectively. This effect was present when associations were assessed by means of faster responding after conditioned stimuli signaling reward (implicit salience) and overt rating of stimulus-reward links (explicit salience). However, unusual feelings and experiences, which are subclinical manifestations of psychotic-like symptoms, were specifically related to irrelevant and illusory stimulus-reward associations (aberrant salience) in PD patients receiving dopamine agonists. The learning of relevant and real stimulus-reward associations (adaptive salience) was not related to unusual experiences. These results suggest that dopamine agonists may increase psychotic-like experiences in young patients with PD, possibly by facilitating dopaminergic transmission in the ventral striatum, which results in aberrant associations between conditioned stimuli and reward.