Posttraumatic functional movement disorders and litigation.

The concept of functional movement disorders has evolved considerably over the past few decades. More specifically, the views on the relation with psychological stressors or personality disorders have substantially changed, emphasizing a shift from the previously dominant dualistic scheme. This evolution is reflected in adaptations to diagnostic criteria and management approaches. Functional movement disorders which arise in a close temporal relationship with a peripheral trauma are specifically challenging with respect to diagnosis and treatment, but similar considerations seem to apply. The relationship of functional disorders with trauma appears to be much closer than is often thought. Clinical and pathophysiological research has identified shared factors underlying functional posttraumatic as well as primary movement disorders. These evolving insights impact on discussions in terms of litigation for compensation after trauma. The literature is reviewed and the consequences for argumentation in litigation are outlined, including ethical and legal considerations. Finally, we formulate a number of recommendations.

Two cases with postural axial tremor: Consider a genetic origin.

We present two cases with postural axial tremor predominantly involving the head, trunk, and shoulders. In the first patient, the postural tremor occurred in multiple attacks a day lasting approximately 10 min. The second patient developed a progressive tremor of his head and arms, worsened during sitting and standing. Electrophysiological supported the postural axial tremor in both patients with a varying 3-10 Hz tremor frequency between different muscles and within the same muscles at different times. Postural axial tremor is a rare and complex movement disorder. The majority of cases are caused by acquired cerebellar pathology. However, isolated cases with underlying genetic disorders are described in literature. Here, we illustrate how to differentiate paroxysmal axial tremor from other axial hyperkinetic movement disorders and extend the genetic heterogeneity of this intriguing movement disorder phenotype.

Subthalamic nucleus activity in the processing of body and mental action verbs in people with Parkinson's disease.

Local field potentials evoked by body action and mental action verbs were recorded in the subthalamic nucleus (STN) of 18 patients with Parkinson's disease through the electrodes implanted for deep brain stimulation. Compared with the medication on-condition, the medication off-condition showed a difference in activity in the early time segments, mainly in the right STN, with larger amplitudes for body action verbs. In the on-condition a similar pattern was detected in the left STN. These patterns of early differences in activity evoked by different types of verbs might indicate the potential of the STN to rapidly detect relevant behavioural clues in verbal content and to integrate these in subsequent cortico-subcortical interactions. In addition, these lateralizations allow speculations about shifts in processing activity correlating with dopaminergic denervation. Whether this detection relies on phonological, semantic or grammatical clues remains an open question.

The white matter architecture underlying semantic processing: A systematic review.

From a holistic point of view, semantic processes are subserved by large-scale subcortico-cortical networks. The dynamic routing of information between grey matter structures depends on the integrity of subcortical white matter pathways. Nonetheless, controversy remains on which of these pathways support semantic processing. Therefore, a systematic review of the literature was performed with a focus on anatomo-functional correlations obtained from direct electrostimulation during awake tumor surgery, and conducted between diffusion tensor imaging metrics and behavioral semantic performance in healthy and aphasic individuals. The 43 included studies suggest that the left inferior fronto-occipital fasciculus contributes to the essential connectivity that allows semantic processing. However, it remains uncertain whether its contributive role is limited to the organization of semantic knowledge or extends to the level of semantic control. Moreover, the functionality of the left uncinate fasciculus, inferior longitudinal fasciculus and the posterior segment of the indirect arcuate fasciculus in semantic processing has to be confirmed by future research.

Electrophysiological registration of phonological perception in the subthalamic nucleus of patients with Parkinson's Disease.

Phonological processing is usually associated with the activation of cortical areas, especially in the left cerebral hemisphere. This study examined if phonologically elicited evoked potentials can be recorded directly from the subthalamic nucleus in patients with Parkinson's Disease (PD). Seven PD patients who had undergone implantation of deep brain electrodes for the stimulation of the subthalamic nucleus were included. Local field potentials were recorded in a pre-attentive auditory phonological task, an attentive auditory phonological discrimination task, and a word recognition task. Auditory evoked potentials related to phonological, but not lexical processing, could be demonstrated in the subthalamic nucleus for all three tasks. Only minor changes were found after levodopa administration. This study demonstrates that the subthalamic nucleus is involved in early phonological perception, which puts the subthalamic nucleus in a position to modify phonological perception in a larger cortico-subcortical network.

Mutations in SACS cause atypical and late-onset forms of ARSACS.

BACKGROUND: Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is a complex neurodegenerative disorder caused by mutations in SACS. The phenotype consists of a childhood-onset triad of cerebellar ataxia, peripheral neuropathy, and pyramidal tract signs. OBJECTIVE: To provide more insight into the prevalence of SACS mutations and the variability of the associated phenotype. METHODS: Mutation screening of SACS by direct sequencing and multiplex amplicon quantification for detection of intragenic copy number variations in a cohort of 85 index patients with phenotypes suggestive for ARSACS. Additional short tandem repeat (STR) marker analysis was performed for haplotype sharing. RESULTS: In 11 families,18 new SACS mutations were found (12.9% of total cohort). Five patients displayed onset ages in adulthood, a feature not known to be associated with ARSACS. The remaining index patients displayed a classic early onset phenotype. Initial phenotypic presentation was atypical in several patients, obscuring the clinical diagnosis. A founder mutation in SACS was identified in 3 Belgian families. In one isolated patient, an intragenic SACS deletion of exons 3-5 was detected. Partial SACS deletions were not previously described. CONCLUSIONS: In this study, we enlarge the ARSACS phenotype and the underlying genetic spectrum of SACS mutations. Patients with ARSACS are more common than previously known and risk underdiagnosis due to late onset age and unusual presentation.

Dystonia in neurodegeneration with brain iron accumulation: outcome of bilateral pallidal stimulation.

Neurodegeneration with brain iron accumulation encompasses a heterogeneous group of rare neurodegenerative disorders that are characterized by iron accumulation in the brain. Severe generalized dystonia is frequently a prominent symptom and can be very disabling, causing gait impairment, difficulty with speech and swallowing, pain and respiratory distress. Several case reports and one case series have been published concerning therapeutic outcome of pallidal deep brain stimulation in dystonia caused by neurodegeneration with brain iron degeneration, reporting mostly favourable outcomes. However, with case studies, there may be a reporting bias towards favourable outcome. Thus, we undertook this multi-centre retrospective study to gather worldwide experiences with bilateral pallidal deep brain stimulation in patients with neurodegeneration with brain iron accumulation. A total of 16 centres contributed 23 patients with confirmed neurodegeneration with brain iron accumulation and bilateral pallidal deep brain stimulation. Patient details including gender, age at onset, age at operation, genetic status, magnetic resonance imaging status, history and clinical findings were requested. Data on severity of dystonia (Burke Fahn Marsden Dystonia Rating Scale-Motor Scale, Barry Albright Dystonia Scale), disability (Burke Fahn Marsden Dystonia Rating Scale-Disability Scale), quality of life (subjective global rating from 1 to 10 obtained retrospectively from patient and caregiver) as well as data on supportive therapy, concurrent pharmacotherapy, stimulation settings, adverse events and side effects were collected. Data were collected once preoperatively and at 2-6 and 9-15 months postoperatively. The primary outcome measure was change in severity of dystonia. The mean improvement in severity of dystonia was 28.5% at 2-6 months and 25.7% at 9-15 months. At 9-15 months postoperatively, 66.7% of patients showed an improvement of 20% or more in severity of dystonia, and 31.3% showed an improvement of 20% or more in disability. Global quality of life ratings showed a median improvement of 83.3% at 9-15 months. Severity of dystonia preoperatively and disease duration predicted improvement in severity of dystonia at 2-6 months; this failed to reach significance at 9-15 months. The study confirms that dystonia in neurodegeneration with brain iron accumulation improves with bilateral pallidal deep brain stimulation, although this improvement is not as great as the benefit reported in patients with primary generalized dystonias or some other secondary dystonias. The patients with more severe dystonia seem to benefit more. A well-controlled, multi-centre prospective study is necessary to enable evidence-based therapeutic decisions and better predict therapeutic outcomes.

Progressive myoclonic epilepsy as an adult-onset manifestation of Leigh syndrome due to m.14487T>C.

BACKGROUND: m.14487T>C, a missense mutation (p.M63V) affecting the ND6 subunit of complex I of the mitochondrial respiratory chain, has been reported in isolated childhood cases with Leigh syndrome (LS) and progressive dystonia. Adult-onset phenotypes have not been reported. OBJECTIVES: To determine the clinical-neurological spectrum and associated mutation loads in an extended m.14487T>C family. METHODS: A genotype-phenotype correlation study of a Belgian five-generation family with 12 affected family members segregating m.14487T>C was carried out. Clinical and mutation load data were available for nine family members. Biochemical analysis of the respiratory chain was performed in three muscle biopsies. RESULTS: Heteroplasmic m.14487T>C levels (36-52% in leucocytes, 97-99% in muscle) were found in patients with progressive myoclonic epilepsy (PME) and dystonia or progressive hypokinetic-rigid syndrome. Patients with infantile LS were homoplasmic (99-100% in leucocytes, 100% in muscle). We found lower mutation loads (between 8 and 35% in blood) in adult patients with clinical features including migraine with aura, Leber hereditary optic neuropathy, sensorineural hearing loss and diabetes mellitus type 2. Despite homoplasmic mutation loads, complex I catalytic activity was only moderately decreased in muscle tissue. INTERPRETATION: m.14487T>C resulted in a broad spectrum of phenotypes in our family. Depending on the mutation load, it caused severe encephalopathies ranging from infantile LS to adult-onset PME with dystonia. This is the first report of PME as an important neurological manifestation of an isolated mitochondrial complex I defect.

The potential value of a pictorial atlas for aid in the visual diagnosis of 123I FP-CIT SPECT scans.

The aim of our study was to evaluate the value of a pictorial atlas of 123I FP-CIT SPECT images for aid in the visual diagnosis. PATIENTS, MATERIALS, METHODS: Sixty patients, of whom 20 were clinically diagnosed as 'non-parkinsonian' and 40 as having Parkinson's disease or any related disorder, were included in the study. An atlas consisting of 12 123I FP-CIT SPECT images was constructed first. Validity of the atlas was investigated by performing a receiver operating characteristic (ROC) analysis with the clinical diagnosis as the gold standard. The remaining 48 SPECT images were visually assessed twice by 5 observers, first with and secondly without consulting the atlas, or vice versa. The added value of the atlas was investigated by comparing the diagnostic accuracy and the interobserver variability for both methods. RESULTS: ROC analysis performed on the atlas yielded an area under the curve of 1 for a threshold discriminating between clinically non-parkinsonian and parkinsonian patients that was situated between image 4 and 5 of the atlas. For the diagnostic accuracy, we found that the area under the ROC curve was systematically higher if observers had access to the atlas compared to when they had not (Wilcoxon's test, p<0.05). Also, the interobserver variability was significantly lower when observers used the atlas when compared to when they did not (p = 0.05). CONCLUSION: Diagnostic accuracy was significantly higher and interobserver variability significantly lower if observers had access to the atlas compared to when they had not. Hence, having a pictorial atlas available may facilitate the visual assessment of 123I FP-CIT SPECT scans.

Catatonia and neuroleptic malignant syndrome: two sides of a coin?

Catatonia was first described by Kahlbaum in 1874. Ever since, the concept of catatonia has been the focus of debate, a major point of discussion being its nosological status. The question rises whether it is to be considered a syndrome with a wide variety of causes and clinical signs or a distinct clinical entity. Since catatonia shares a number of symptoms with the neuroleptic malignant syndrome (NMS) and similar treatments can be used in both conditions, it has also been suggested that NMS and catatonia are two variants of the same disorder In this article we describe five cases of catatonia and NMS in order to approach this nosological question. The clinical similarity between both syndromes is demonstrated in our cases. On the level of pathophysiology however, catatonia and NMS are quite different, with catatonia rather being a cortical psychomotor syndrome and NMS a subcortical motor disorder. Similarities can be explained by means of well-known models of basal ganglia function. The nosological problem, however; can only be resolved when the concept of catatonia is better defined.

Saccadic ping pong gaze in coma.

In this report, we describe the peculiar eye movements of a young man who became comatose after a head injury. The eyes moved rhythmically from one side to another, without pausing in the lateral positions. This phenomenon has been described as "ping pong gaze" (PPG), referring to short-cycling periodic alternating gaze with smooth eye deviations. In the present patient, however, a saccadic type of PPG could be confirmed by oculography. Possible clinical and pathophysiological implications are discussed.

Comparison of age of onset and development of motor complications between smokers and non-smokers in Parkinson's disease.

BACKGROUND: There is growing evidence from case-control and from cohort studies that smoking is inversely related to the risk of developing Parkinson's disease (PD). However, it is still controversial if PD starts at an older age in ever-smoking patients compared to never-smoking ones. PATIENTS AND METHODS: The present retrospective study compares in a large series of 512 out-patients, collected over the last 24 years, the age of onset of the complaints, the age at which PD was diagnosed and the start of levodopa treatment between ever- and never-smokers. Also, the occurrence of long-term side-effects of the drug was evaluated. 184 PD patients with a history of smoking were compared with 328 who had never smoked. The subgroups with and without a family history of PD were analysed separately. RESULTS: In the overall ever-smoking group, as well as in the subgroup without a family history, the onset of the disease and the time of the diagnosis of PD and the time at which levodopa was started occurred at an older age than in the never-smoking group. This difference could not be demonstrated in the patients with a family history, due to the low number of cases and the lack of statistical power. Although the follow-up period was the same in both study groups, motor fluctuations and dyskinesia were more frequent and appeared earlier after levodopa treatment in the non-smoking compared to the ever-smoking PD patients. Only for cognitive impairment there was a non-significant trend in the smoking group. CONCLUSION: The present study confirms the protective action of smoking on PD and also suggests some modulating effect of smoking on the dopaminergic system.

Subacute Hashimoto's encephalopathy, treated with plasmapheresis.

We report a patient with subacute diffuse encephalopathy characterised by rapidly progressive dementia with visual hallucinations, myoclonus and generalised seizures. She was euthyroid but showed high serum levels of thyreoglobulin and thyreoperoxidase antibodies. Hashimoto's encephalopathy was diagnosed. MRI of the brain in the acute phase demonstrated no structural abnormalities. However in the mesotemporal regions and the anterior parts of the brain, a decrease of the N-acetylaspartate and an increase of the Choline-containing compounds was found on MRI-spectroscopy. Reversal of these abnormalities was demonstrated a few months later after starting therapy. Plasmapheresis resulted in normalisation of serum levels of the antibodies and rapid clinical improvement. This observation supports the idea that a correlation exists between the serum levels of the thyroid auto-antibodies and the course of the clinical illness.

The pathophysiology of motor symptoms in Parkinson's disease.

This review focuses on some of the known and hypothetical pathophysiological mechanisms underlying the motor symptoms in Parkinson's disease (PD). Current views on these mechanisms have largely been influenced by models of basal ganglia functioning and dysfunctioning. These models have allowed to explain some clinical findings and to predict a number of results of basal ganglia surgery in movement disorders. However, neurophysiological studies as well as neurochemical data have broadened our vision on basal ganglia functioning and dysfunctioning in PD. Moreover, these more fundamental insights in basal ganglia functioning allow new concepts on the development of treatment strategies, and on the prevention of motor fluctuations in PD.

Donepezil in the treatment of mild to moderate Alzheimer's disease: report of a Belgian multicenter study.

In this report the results of a Belgian multicenter 24-week open-label study with donepezil in the treatment of mild to moderate Alzheimer's disease are described. Efficacy and safety were evaluated in a sample of 200 patients recruited in 25 Belgian centers. No significant changes could be found in cognition and behaviour over this 6-month period. Changes in daily functioning were small. Safety data were comparable to those reported in international trials. These results suggest that the findings of more robust double-blind, placebo-controlled studies can be confirmed in real life situations.

Predictors of cognitive impairment in advanced Parkinson's disease.

OBJECTIVE: To investigate the cognitive profile of patients with idiopathic Parkinson's disease and to determine the demographic and medical variables that contribute to the cognitive outcome. DESIGN: Retrospective cohort analysis. METHODS: 100 patients with idiopathic Parkinson's disease were given a neuropsychological test battery investigating attention, memory, and visuospatial and executive functions. Test performance was compared against normative data, and linear regression determined significant predictors of cognitive impairment from a set of demographic and disease course variables. RESULTS: Frontal-type cognitive dysfunction was widespread in patients with advanced Parkinson's disease. Attention and memory were mildly to moderately impaired, whereas visuospatial function showed only subtle impairment. Older age and tremor at onset were significant predictors of poor cognitive performance. CONCLUSIONS: The observed cognitive impairment in patients with advanced Parkinson's disease is more than expected for normal aging. Although in apparent contrast with most previous research, reporting a greater risk of cognitive dysfunction in Parkinson's disease patients with predominant akinesia/rigidity, tremor at onset may be a marker for more widespread brain pathology that contributes to an increased risk of cognitive impairment.

Regional cerebral blood flow and episodic memory in Parkinson's disease: a single photon emission tomography study.

In this paper we examined 46 nondemented Parkinson's disease (PD) patients by means of perfusion single photon emission computed tomography (SPECT) and neuropsychological testing. The aim was to detect correlations of regional cerebral blood flow with episodic memory performance, using an operator-independent technique for the analysis of SPECT data. A significant positive correlation was found between prefrontal blood flow and episodic memory performances. However, age was the most important determinant of memory scores. Age also correlated significantly negatively with prefrontal perfusion. Our methodology also allowed detection of an inverse correlation of left medial temporal lobe perfusion with the memory score. This had not been found in previous studies and might indicate compensatory mechanisms in the brain of PD patients. It is concluded that episodic memory in nondemented PD patients is most dependent on the effects of aging and that the aging effects on cerebral perfusion in the PD brain parallel to a large extent the findings in normal controls.