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Attention plays a crucial role in functional neurological disorders. Attention to the symptoms leads to their exacerbation and distraction to their improvement or even transitory disappearance. Objective: The aim was to test if the alerting, orienting and particularly the executive aspect of attention are affected in functional movement disorders. Methods: Thirty patients with a functional movement disorder, 30 patients with an organic movement disorder and 30 healthy controls performed the attention network test. Results: The alerting and orienting effects were normal, but executive control of attention under conflict was abnormal in patients with functional movement disorders, compared to patients with an organic movement disorder and healthy controls. Conclusion: Executive dysfunction seems to be an important secondary feature of functional movement disorders, due to the overutilization of attentional resources for explicit movement control. Furthermore, it provides an explanation for seemingly unrelated symptoms commonly associated with functional movement disorders, such as concentration difficulties and fatigue.

BACKGROUND: Surround inhibition (SI) in the motor system has been described to be decreased in patients with focal hand dystonia (FHD) but no evidence currently exists for patients with cervical dystonia (CD). OBJECTIVE: To characterise the SI profiles in three groups of participants: healthy volunteers, patients with FHD and patients with CD. To provide sample size calculations for future studies. METHODS: SI was assessed using Transcranial Magnetic Stimulation (TMS) in 31 right-handed healthy participants, 11 patients with CD and 12 patients with FHD. In addition data of SI in patients with FHD were extracted from previously published and analysed for sample size calculations and assessment of SI variability. RESULTS: No statistically significant difference in SI was found amongst the groups (healthy, FHD, CD). Analysis of combined current and previous data suggests that our study and all prior studies were underpowered. At least 26 participants in each group are required for a simple comparison of two groups. Analysis of published data indicated that SI is more variable in FHD patients compared to healthy controls. CONCLUSIONS: The highly variable SI in patients with dystonia can confound statistical comparisons of mean differences. Larger studies are needed to assess SI in dystonia and to explore the origins of its variability.

Contains fulltext : 167700.pdf (Publisher’s version ) (Open Access) Chorea is a hyperkinetic movement disorder resulting from dysfunction of striatal medium spiny neurons (MSNs), which form the main output projections from the basal ganglia. Here, we used whole-exome sequencing to unravel the underlying genetic cause in three unrelated individuals with a very similar and unique clinical presentation of childhood-onset chorea and characteristic brain MRI showing symmetrical bilateral striatal lesions. All individuals were identified to carry a de novo heterozygous mutation in PDE10A (c.898T>C [p.Phe300Leu] in two individuals and c.1000T>C [p.Phe334Leu] in one individual), encoding a phosphodiesterase highly and selectively present in MSNs. PDE10A contributes to the regulation of the intracellular levels of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP). Both substitutions affect highly conserved amino acids located in the regulatory GAF-B domain, which, by binding to cAMP, stimulates the activity of the PDE10A catalytic domain. In silico modeling showed that the altered residues are located deep in the binding pocket, where they are likely to alter cAMP binding properties. In vitro functional studies showed that neither substitution affects the basal PDE10A activity, but they severely disrupt the stimulatory effect mediated by cAMP binding to the GAF-B domain. The identification of PDE10A mutations as a cause of chorea further motivates the study of cAMP signaling in MSNs and highlights the crucial role of striatal cAMP signaling in the regulation of basal ganglia circuitry. Pharmacological modulation of this pathway could offer promising etiologically targeted treatments for chorea and other hyperkinetic movement disorders.

Background: Movement disorders associated with exposure to antipsychotic drugs are common and stigmatising but underdiagnosed. Aims: To develop and evaluate a new clinical procedure, the ScanMove instrument, for the screening of antipsychotic-associated movement disorders for use by mental health nurses. Method: Item selection and content validity assessment for the ScanMove instrument were conducted by a panel of neurologists, psychiatrists and a mental health nurse, who operationalised a 31-item screening procedure. Interrater reliability was measured on ratings for 30 patients with psychosis from ten mental health nurses evaluating video recordings of the procedure. Criterion and concurrent validity were tested comparing the ScanMove instrument-based rating of 13 mental health nurses for 635 community patients from mental health services with diagnostic judgement of a movement disorder neurologist based on the ScanMove instrument and a reference procedure comprising a selection of commonly used rating scales. Results: Interreliability analysis showed no systematic difference between raters in their prediction of any antipsychotic-associated movement disorders category. On criterion validity testing, the ScanMove instrument showed good sensitivity for parkinsonism (90%) and hyperkinesia (89%), but not for akathisia (38%), whereas specificity was low for parkinsonism and hyperkinesia, and moderate for akathisia. Conclusions: The ScanMove instrument demonstrated good feasibility and interrater reliability, and acceptable sensitivity as a mental health nurse-administered screening tool for parkinsonism and hyperkinesia. Declaration of interest: None.

N.A.

Background: The onset of multiple system atrophy (MSA) before age 40 years is referred to as “young-onset MSA.” We identified clinical and pathological characteristics that might help with its early diagnosis and distinction from young-onset Parkinson's disease and late-onset MSA. Methods: We reviewed the available clinical and pathological features in cases that fulfilled consensus criteria for diagnosis of probable MSA or had autopsy confirmed MSA with an onset before age 40 years and compared the clinical features with 16 autopsy confirmed cases with young-onset Parkinson's disease and a large published series of late-onset MSA from the European MSA Study Group. Results: We identified 22 patients with young-onset MSA, 8 of whom had available pathology. The mean age of onset was 36.7 years (standard deviation 2.3). Levodopa-induced dyskinesia was more common, whereas myoclonus and pyramidal signs were less common in young-onset Parkinson's disease when compared with young-onset MSA. Dystonia, levodopa responsiveness, levodopa-induced dyskinesia, and pyramidal signs were more common (P

Movement disorders are a common feature of autoantibody-associated diseases. Balint et al. provide a novel phenotype-oriented algorithmic approach to guide diagnosis. They review the underlying pathophysiology and point out parallels between immune-mediated and genetic conditions presenting with similar phenotypes. They consider future directions such as personalised immunotherapy., Movement disorders are a prominent and common feature in many autoantibody-associated neurological diseases, a group of potentially treatable conditions that can mimic infectious, metabolic or neurodegenerative disease. Certain movement disorders are likely to associate with certain autoantibodies; for example, the characteristic dyskinesias, chorea and dystonia associated with NMDAR antibodies, stiff person spectrum disorders with GAD, glycine receptor, amphiphysin or DPPX antibodies, specific paroxysmal dystonias with LGI1 antibodies, and cerebellar ataxia with various anti-neuronal antibodies. There are also less-recognized movement disorder presentations of antibody-related disease, and a considerable overlap between the clinical phenotypes and the associated antibody spectra. In this review, we first describe the antibodies associated with each syndrome, highlight distinctive clinical or radiological ‘red flags’, and suggest a syndromic approach based on the predominant movement disorder presentation, age, and associated features. We then examine the underlying immunopathophysiology, which may guide treatment decisions in these neuroimmunological disorders, and highlight the exceptional interface between neuronal antibodies and neurodegeneration, such as the tauopathy associated with IgLON5 antibodies. Moreover, we elaborate the emerging pathophysiological parallels between genetic movement disorders and immunological conditions, with proteins being either affected by mutations or targeted by autoantibodies. Hereditary hyperekplexia, for example, is caused by mutations of the alpha subunit of the glycine receptor leading to an infantile-onset disorder with exaggerated startle and stiffness, whereas antibodies targeting glycine receptors can induce acquired hyperekplexia. The spectrum of such immunological and genetic analogies also includes cerebellar ataxias and some encephalopathies. Lastly, we discuss how these pathophysiological considerations could reflect on possible future directions regarding antigen-specific immunotherapies or targeting the pathophysiological cascades downstream of the antibody effects.

BACKGROUND: Consensus criteria for classifying tremor disorders were published by the International Parkinson and Movement Disorder Society in 1998. Subsequent advances with regard to essential tremor, tremor associated with dystonia, and other monosymptomatic and indeterminate tremors make a significant revision necessary. OBJECTIVES: Convene an international panel of experienced investigators to review the definition and classification of tremor. METHODS: Computerized MEDLINE searches in January 2013 and 2015 were conducted using a combination of text words and MeSH terms: "tremor", "tremor disorders", "essential tremor", "dystonic tremor", and "classification" limited to human studies. Agreement was obtained using consensus development methodology during four in-person meetings, two teleconferences, and numerous manuscript reviews. RESULTS: Tremor is defined as an involuntary, rhythmic, oscillatory movement of a body part and is classified along two axes: Axis 1-clinical characteristics, including historical features (age at onset, family history, and temporal evolution), tremor characteristics (body distribution, activation condition), associated signs (systemic, neurological), and laboratory tests (electrophysiology, imaging); and Axis 2-etiology (acquired, genetic, or idiopathic). Tremor syndromes, consisting of either isolated tremor or tremor combined with other clinical features, are defined within Axis 1. This classification scheme retains the currently accepted tremor syndromes, including essential tremor, and provides a framework for defining new syndromes. CONCLUSIONS: This approach should be particularly useful in elucidating isolated tremor syndromes and syndromes consisting of tremor and other signs of uncertain significance. Consistently defined Axis 1 syndromes are needed to facilitate the elucidation of specific etiologies in Axis 2. © 2017 International Parkinson and Movement Disorder Society.

Histone lysine methylation, mediated by mixed-lineage leukemia (MLL) proteins, is now known to be critical in the regulation of gene expression, genomic stability, cell cycle and nuclear architecture. Despite MLL proteins being postulated as essential for normal development, little is known about the specific functions of the different MLL lysine methyltransferases. Here we report heterozygous variants in the gene KMT2B (also known as MLL4) in 27 unrelated individuals with a complex progressive childhood-onset dystonia, often associated with a typical facial appearance and characteristic brain magnetic resonance imaging findings. Over time, the majority of affected individuals developed prominent cervical, cranial and laryngeal dystonia. Marked clinical benefit, including the restoration of independent ambulation in some cases, was observed following deep brain stimulation (DBS). These findings highlight a clinically recognizable and potentially treatable form of genetic dystonia, demonstrating the crucial role of KMT2B in the physiological control of voluntary movement.

The aim of this study is to evaluate the brainstem function in DYT1 carriers manifesting clinical dystonia (MDYT1) and those without clinical symptoms (NMDYT1). Motor cortical inhibition and plasticity were found to be abnormal in MDYT1, whereas these were less abnormal in NMDYT1. However, the spinal reciprocal inhibition was abnormal in MDYT1, but normal in NMDYT1. Moreover, protein accumulation and perinuclear inclusion bodies were found in the brainstem, but not in other brain areas, in DYT1 patients. Therefore, we designed this study to investigate the brainstem physiology using the blink reflex (BR) recovery cycle test in MDYT1 and NMDYT1. We recruited eight MDYT1, five NMDYT1, and nine age-matched healthy controls. The BR recovery cycle was assessed with paired stimuli that induced the BR in a random order at interstimulus intervals of 250, 500, and 1000 ms. A two-way analysis of variance showed a significant difference between MDYT1, NMDYT1, and the healthy control (P=0.004). Post-hoc analysis showed that this was because of a significantly lower inhibition of R2 in MDYT1 and NMDYT1 compared with the controls (two-way analysis of variance: P=0.003 and 0.021, respectively). There was no difference between MDYT1 and NMDYT1 (P=0.224). The tested brainstem circuits were equally involved in MDYT1 and NMDYT1. The finding is in agreement with the pathological findings in DYT1 carriers. Together with previous findings in the motor cortex and the spinal cord, the brainstem may lie closer to the pathogenesis of dystonia than the motor cortex in DYT1 gene carriers.

It was reported recently that specific features in the frequency analysis of electromyographic (EMG) activity in the sternocleidomastoid (SCM) and splenius (SPL) muscles were able to distinguish between rotational idiopathic cervical dystonia (CD) and voluntary torticollis in individual subjects. Those with CD showed an abnormal drive to muscles at 5 to 7 Hz and an absence of the normal 10 to 12 Hz peak in the autospectrum of SPL. We sought to determine whether the same abnormalities in the frequency domain are found in complex CD, in which the head is displaced in more than two planes. EMG activity was recorded in the SCM, SPL, trapezius, and levator scapulae muscles bilaterally in 10 patients with complex CD. Frequency analysis of EMG was compared with conventional clinical and polymyographic assessment. The antospectrum of SPL during free dystonic contraction showed an absence of a significant peak at 10 to 12 Hz in 8 of the 10 patients. The presence of a 5 to 7 Hz frequency drive showed a significant association with muscle pairs determined as dystonic by means of polymyography (P

Orthostatic tremor (OT) is a rare condition characterized by unsteadiness when standing still that is relieved when sitting or walking and is thought to arise from a central generator in the cerebellum or brainstem. OT is considered to be a distinct, discrete condition, and little is known about its demographic characteristics, natural history, associated features, and treatment response. We have reviewed these aspects in 41 OT patients fulfilling current diagnostic criteria, seen at our institution between 1986 and 2001. We classified 31 (75%) as having idiopathic "primary OT" either with (n = 24) or without an associated postural arm tremor. We found that 10 of 41 (25%) cases had additional neurological features, and we defined this group as having "OT plus" syndrome. Of these 10, 6 had parkinsonism; 4 of these had typical Parkinson's disease (PD), 1 had vascular and 1 had drug-induced parkinsonism. Among the remaining 4 patients, 2 had restless legs syndrome (RLS), 1 had tardive dyskinesia, and 1 orofacial dyskinesias of uncertain etiology. One patient with PD and the patient with vascular parkinsonism also had RLS. Age at onset was significantly earlier in the "primary OT" (mean +/- SD, 50.4 +/- 15.1) than in the "OT plus" (61.8 +/- 6.4; z = 2.7; P =.006) group. In 7 of the 10 "OT plus" patients, OT leg symptoms preceded the onset of additional neurological features. OT appeared to be underdiagnosed, and on average, it took 5.7 years from the initial complaints until a diagnosis was made. In general, treatment response to a variety of drugs such as clonazepam, primidone, and levodopa was poor. In most cases, OT symptoms remain relatively unchanged over the years, but in 6 of 41 cases (15%), the condition gradually worsened over the years, and in some of these cases, symptoms spread proximally to involve the trunk and arms. OT may not be a discrete disorder as commonly believed and associated features like parkinsonism present in nearly 25% of cases. Dopaminergic dysfunction may have a role in the pathophysiology of this disorder.

Spinocerebellar ataxia 6 (SCA6) is a hereditary disease characterized by a trinucleotide repeat expansion in the CACNA1A gene and late-onset bilateral cerebellar atrophy. It is unclear if there is significant pathology outside of the cerebellum. We used transcranial magnetic stimulation to assess sensorimotor cortical circuits and cortical plasticity in 8 SCA6 patients and 8 age-matched controls. Behavioral performance was assessed using a rhythmic tapping task. Neurophysiological measures of SCA6 patients showed a prolonged cortical silent period (CSP) but normal MEP recruitment curve, short-latency afferent inhibition, long-latency afferent inhibition and ipsilateral silent period. Paired-associative stimulation induction also increased motor-evoked potentials normally. SCA6 patients had greater variability with cued rhythmic tapping than normals and deteriorated when the cue was removed; in comparison, normal subjects had similar variability between cued and uncued rhythmic tapping. Analysis using a Wing-Kristofferson timing model indicated that both clock variance and motor delay variance were abnormal. Conclusion. In SCA6, the circuits for sensorimotor integration and the mechanisms for LTP-like plasticity in the sensorimotor cortex are unimpaired. A prolonged CSP in SCA6 just like in other cerebellar atrophies would suggest that this neurophysiological change typifies cerebellar dysfunction.

BackgroundA number of neurophysiological abnormalities have been described in patients with Parkinson's disease, but very few longitudinal studies of how these change with disease progression have been reported. We describe measures of motor cortex inhibition and plasticity at 6 and 12 mo in 12 patients that we previously reported at initial diagnosis. Given the well-known interindividual variation in these measures, we were particularly concerned with the within-subject changes over time. MethodsPatients were assessed clinically, and transcranial magnetic stimulation (TMS) was used to measure motor cortical excitability, inhibition (short interval intracortical inhibition, cortical silent period), and plasticity (response to excitatory paired associative stimulation protocol) in both hemispheres. All measurements were performed 6 mo and 12 mo after the baseline experiments. ResultsAsymmetry in clinical motor symptoms was reflected in asymmetry of plasticity and inhibition. In the group as a whole, little change was seen in any of the parameters over 12 mo. However, analysis of within-individual data showed clear correlations between changes in clinical asymmetry and asymmetry of response to paired associative stimulation protocol and cortical silent period. ConclusionsLongitudinal changes in cortical silent period and response to paired associative stimulation protocol in Parkinson's disease reflect dynamic effects on motor cortex that are related to progression of motor signs. They are useful objective markers of early disease progression that could be used to detect effects of disease-modifying therapies. The decline in heightened plasticity that was present at disease onset may reflect failure of compensatory mechanisms that maintained function in the preclinical state. (c) 2015 International Parkinson and Movement Disorder Society

Dystonia is a common movement disorder. A number of monogenic causes have been identified. However, the majority of dystonia cases are not explained by single gene defects. Cervical dystonia is one of the commonest forms without genetic causes identified. This pilot study aimed to identify large effect-size risk loci in cervical dystonia. A genomewide association study (GWAS) was performed. British resident cervical dystonia patients of European descent were genotyped using the Illumina-610-Quad. Comparison was made with controls of European descent from the Wellcome Trust Case Control Consortium using logistic regression algorithm from PLINK. SNPs not genotyped by the array were imputed with 1000 Genomes Project data using the MaCH algorithm and minimac. Postimputation analysis was done with the mach2dat algorithm using a logistic regression model. After quality control measures, 212 cases were compared with 5173 controls. No single SNP passed the genomewide significant level of 5 × 10(-8) in the analysis of genotyped SNP in PLINK. Postimputation, there were 5 clusters of SNPs that had P value

Motivational influence on bradykinesia in Parkinson's disease may be observed in situations of emotional and physical stress, a phenomenon known as paradoxical kinesis. However, little is known about motivational modulation of movement speed beyond these extreme circumstances. In particular, it is not known if motivational factors affect movement speed by improving movement preparation/initiation or execution (or both) and how this effect relates to the patients' medication state. In the present study, we tested if provision of motivational incentive through monetary reward would speed-up movement initiation and/or execution in Parkinson's disease patients and if this effect depended on dopaminergic medication. We studied the effect of monetary incentive on simple reaction time in 11 Parkinson's disease patients both "off" and "on" dopaminergic medication and in 11 healthy participants. The simple reaction time task was performed across unrewarded and rewarded blocks. The initiation time and movement time were quantified separately. Anticipation errors and long responses were also recorded. The prospect of reward improved initiation times in Parkinson's disease patients both "off" and "on" dopaminergic medication, to a similar extent as in healthy participants. However, for "off" medication, this improvement was associated with increased frequency of anticipation errors, which were eliminated by dopamine replacement. Dopamine replacement had an additional, albeit small effect, on reward-related improvement of movement execution. Motivational strategies are helpful in overcoming bradykinesia in Parkinson's disease. Motivational factors may have a greater effect on bradykinesia when patients are "on" medication, as dopamine appears to be required for overcoming speed-accuracy trade-off and for improvement of movement execution. Thus, medication status should be an important consideration in movement rehabilitation programmes for patients with Parkinson's disease. © 2014 The Author(s).

Dystonia type 4 (DYT4) was first described in a large family from Heacham in Norfolk with an autosomal dominantly inherited whispering dysphonia, generalized dystonia, and a characteristic hobby horse ataxic gait. We carried out a genetic linkage analysis in the extended DYT4 family that spanned 7 generations from England and Australia, revealing a single LOD score peak of 6.33 on chromosome 19p13.12-13. Exome sequencing in 2 cousins identified a single cosegregating mutation (p.R2G) in the β-tubulin 4a (TUBB4a) gene that was absent in a large number of controls. The mutation is highly conserved in the β-tubulin autoregulatory MREI (methionine-arginine-glutamic acid-isoleucine) domain, highly expressed in the central nervous system, and extensive in vitro work has previously demonstrated that substitutions at residue 2, specifically R2G, disrupt the autoregulatory capability of the wild-type β-tubulin peptide, affirming the role of the cytoskeleton in dystonia pathogenesis.

The syndrome of deafness-dystonia is rare and refers to the association of hearing impairment and dystonia when these are dominant features of a disease. Known genetic causes include Mohr-Tranebjaerg syndrome, Woodhouse-Sakati syndrome, and mitochondrial disorders, but the cause frequently remains unidentified. The aim of the current study was to better characterize etiological and clinical aspects of deafness-dystonia syndrome. We evaluated 20 patients with deafness-dystonia syndrome who were seen during the period between 1994 and 2011. The cause was identified in only 7 patients and included methylmalonic aciduria, meningoencephalitis, perinatal hypoxic-ischemic injury, large genomic deletion on chromosome 7q21, translocase of inner mitochondrial membrane 8 homolog A (TIMM8A) mutation (Mohr-Tranebjaerg syndrome), and chromosome 2 open reading frame 37 (C2orf37) mutation (Woodhouse-Sakati syndrome). The age of onset and clinical characteristics in these patients varied, depending on the etiology. In 13 patients, the cause remained unexplained despite extensive work-up. In the group of patients who had unknown etiology, a family history for deafness and/or dystonia was present the majority of patients, suggesting a strong genetic component. Sensory-neural deafness always preceded dystonia. Two clinical patterns of deafness-dystonia syndrome were observed: patients who had an onset in childhood had generalized dystonia (10 of 13 patients) with frequent bulbar involvement, whereas patients who had a dystonia onset in adulthood had segmental dystonia (3 of 13 patients) with the invariable presence of laryngeal dystonia. Deafness-dystonia syndrome is etiologically and clinically heterogeneous, and most patients have an unknown cause. The different age at onset and variable family history suggest a heterogeneous genetic background, possibly including currently unidentified genetic conditions.

Objective The current criteria for conversion disorder in the Diagnostic and Statistical Manual of Mental Disorders rely on the assumption that neurological disorders can be distinguished from conversion disorders through clinical assessment. This study aims to assess inter-rater agreement among clinicians with experience in the diagnosis of various hyperkinetic jerky movements, including psychogenic jerks.Methods 60 patients with psychogenic jerks, myoclonus or tics were rated by international experts using a standardised survey resembling daily clinical practice. The survey included the following diagnostic steps: a short video offering a visual impression of the patients and their jerky movements, medical history, neurological examination (on video), additional investigations and the findings of a standardised psychiatric interview. The diagnosis and diagnostic certainty were scored after each step.Results After all clinical information was given, moderate inter-rater agreement was reached (kappa=0.56 +/- 0.1) with absolute agreement (100%) of experts on the diagnosis in 12 (20%) patients and reasonable agreement (>75%) in 43 (72%) patients. Psychiatric evaluation did not contribute to inter-rater agreement or diagnostic certainty.Conclusions Our findings illustrate the fact that experienced movement disorder specialists moderately agree on the clinical diagnosis of jerky movements. Clinical assessment, especially by a team of clinicians in challenging individual cases, might improve diagnostic agreement.

BACKGROUND: Approximately 10% of patients clinically diagnosed with early Parkinson's disease (PD) subsequently have normal dopaminergic functional imaging. Transcranial sonography (TCS) has been shown to detect midbrain hyperechogenicity in approximately 90% of Parkinson's disease (PD) patients and 10% of the healthy population. The aim of this study was to investigate the prevalence of midbrain hyperechogenicity in patients with suspected parkinsonism and scans without evidence of dopaminergic deficit (SWEDD), in comparison to PD patients. METHODS: TCS was performed in 14 patients with SWEDD and 19 PD patients. RESULTS: There was a significantly increased area of echogenicity in the PD group (0.24 ± 0.06 cm(2) ), compared to the group of patients with SWEDD (0.13 ± 0.06 cm(2) ; P < 0.001). One (9.1%) of these patients, compared to 14 (82.5%) of the PD patients, was found to have hyperechogenicity (P < 0.001). CONCLUSIONS: We conclude that TCS is useful to distinguish PD patients from patients with suspected parkinsonism and SWEDD.

A confident clinical diagnosis of psychogenic tremor is often possible, but, in some cases, a "laboratory-supported" level of certainty would aid in early positive diagnosis. Various electrophysiological tests have been suggested to identify patients with psychogenic tremor, but their diagnostic reliability has never been assessed "head to head" nor compared to forms of organic tremor other than essential tremor or PD. We compared baseline tremor characteristics (e.g., frequency and amplitude) as well as electrophysiological tests previously reported to distinguish psychogenic and organic tremor in a cohort of 13 patients with psychogenic tremor and 25 patients with organic tremor, the latter including PD, essential-, dystonic-, and neuropathic tremors. We assessed between-group differences and calculated sensitivity and specificity for each test. A number of tests, including entrainment or frequency changes with tapping, pause of tremor during contralateral ballistic movements, increase in tremor amplitude with loading, presence of coherence, and tonic coactivation at tremor onset, revealed significant differences on a group level, but there was no single test with adequate sensitivity and specificity for separating the groups (33%-77% and 84%-100%, respectively). However, a combination of electrophysiological tests was able to distinguish psychogenic and organic tremor with excellent sensitivity and specificity. A laboratory-supported level of diagnostic certainty in psychogenic tremor is likely to require a battery of electrophysiological tests to provide sufficient specificity and sensitivity. Our data suggest such a battery that, if supported in a prospective study, may form the basis of laboratory-supported criteria for the diagnosis of psychogenic tremor.

Primary lateral sclerosis (PLS), the upper motor neurone variant of motor neurone disease, is characterized by progressive spinal or bulbar spasticity with minimal motor weakness. Rarely, PLS may present with clinical features resembling parkinsonism resulting in occasional misdiagnosis as one of the atypical parkinsonian syndromes. Here we describe five patients initially referred with a diagnosis of levodopa-unresponsive atypical parkinsonism (n = 4) or primary progressive multiple sclerosis (n = 1), but subsequently found to have features consistent with PLS instead. Onset age varied from 49 to 67 years. Unilateral limb slowness or clumsiness was the initial complaint in four, and bulbar symptoms in one. Repeated finger/foot tapping was slow in all five, but without fatiguing or decrement. Spasticity with hyperreflexia, exaggerated jaw jerk and extensor plantar responses were eventually seen in all patients. Anterior horn cell involvement developed in three cases. Early gait disturbances resulting in falls were seen in all patients and none of them responded to dopaminergic medications. Two patients underwent dopamine transporter (DaT) SPECT scanning with normal results. Other features included emotional lability (n = 5) and cognitive impairment involving frontal subcortical systems (n = 1). In conclusion, these cases represent a subgroup of PLS patients in whom pyramidal slowness may be mistaken for akinesia, and spasticity misconstrued as rigidity, leading to an erroneous diagnosis of atypical parkinsonism. However, the absence of fatiguing and decrement on repeated finger/foot tapping should help to distinguish these patients from the true atypical parkinsonian syndromes. (c) 2007 Movement Disorder Society.