BACKGROUND:Five cases of tremor only upon smiling have been reported where no facial tremor is present at rest, when talking, or with full smile. CASES:This report highlights four cases of tremor upon partial smiling, discusses the phenomenology of smiling tremor, and reviews the current literature. Four subjects with lower facial tremor present only upon smiling underwent movement disorders evaluation with video. Tremor frequencies were determined by parsing the video clips into 1-second intervals and averaging the number of oscillations per interval and were determined to be high-frequency 8 to 10 Hz irregular facial tremors with harmonic variations upon moderate effort in all cases. Slight or full-effort smiling did not elicit facial muscle oscillations. Subjects had no other signs of tremor, dystonia, or parkinsonism on examination or in family history. CONCLUSIONS:Tremor upon smiling only, or isolated smiling tremor, is a unique task- and position-specific tremor of the facial musculature.

Enhanced cerebellar oscillations have recently been identified in essential tremor (ET) patients as a key pathophysiological change. Since ET is considered a heterogeneous group of diseases, we investigated whether cerebellar oscillations differ in ET subtypes (familial vs. sporadic). This study aims to determine cerebellar physiology in familial and sporadic ET. Using surface electroencephalogram, we studied cerebellar physiology in 40 ET cases (n = 22 familial and n = 18 sporadic) and 20 age-matched controls. Both familial and sporadic ET cases had an increase in the intensity of cerebellar oscillations when compared to controls. Interestingly, cerebellar oscillations correlated with tremor severity in familial ET but not in sporadic ET. Our study demonstrated that ET cases have enhanced cerebellar oscillations, and the different relationships between cerebellar oscillations and tremor severity in familial and sporadic ET suggest diverse cerebellar pathophysiology.

OBJECTIVE:To determine whether spiral analysis can monitor the effects of deep brain stimulation (DBS) in Parkinson disease (PD) and provide a window on clinical features that change post-operatively. Clinical evaluation after DBS is subjective and insensitive to small changes. Spiral analysis is a computerized test that quantifies kinematic, dynamic, and spatial aspects of spiral drawing. Validated computational indices are generated and correlate with a range of clinically relevant motor findings. These include measures of overall clinical severity (Severity), bradykinesia and rigidity (Smoothness), amount of tremor (Tremor), irregularity of drawing movements (Variability), and micrographia (Tightness). METHODS:We retrospectively evaluated the effect of subthalamic nucleus (STN) (n = 66) and ventral intermediate thalamus (Vim) (n = 10) DBS on spiral drawing in PD subjects using spiral analysis. Subjects freely drew ten spirals on plain paper with an inking pen on a graphics tablet. Five spiral indices (Severity, Smoothness, Tremor, Variability, Tightness) were calculated and compared pre- and post-operatively using Wilcoxon-rank sum tests, adjusting for multiple comparisons. RESULTS:Severity improved after STN and Vim DBS (p < 0.005). Smoothness (p < 0.01) and Tremor (p < 0.02) both improved after STN and Vim DBS. Variability improved only with Vim DBS. Neither STN nor Vim DBS significantly changed Tightness. CONCLUSIONS:All major spiral indices, except Tightness, improved after DBS. This suggests spiral analysis monitors DBS effects in PD and provides an objective window on relevant clinical features that change post-operatively. It may thus have utilization in clinical trials or investigations into the neural pathways altered by DBS. The lack of change in Tightness supports the notion that DBS does not improve micrographia.

Primary lateral sclerosis (PLS) is a motor neuron disease characterized by spinobulbar spasticity, absence of progressive lower motor neuron (LMN) dysfunction and marked by a slow functional decline. Electromyography is essential to exclude significant LMN involvement, particularly in the context of distinguishing PLS from amyotrophic lateral sclerosis (ALS), given that the prognosis is substantially better, and respiratory complications are unusual, in PLS. Nevertheless, minor neurogenic changes and occasional fasciculation potentials can be observed in PLS. The most useful technique for the objective assessment of upper motor neuron (UMN) dysfunction is transcranial magnetic stimulation (TMS), which in PLS is characterized by a high cortical threshold and delayed central conduction times. TMS is sensitive to identify cortical dysfunction in PLS and might have potential for monitoring UMN function in longitudinal studies and in clinical trials. The findings of TMS need to be interpreted in the context of the clinical presentation and phenotype, particularly in the differentiation between PLS and ALS. While other neurophysiological techniques have been investigated, studies to date have tended to involve small patient cohorts and as such, their value in distinguishing PLS from ALS remains unclear.

Background: Holmes tremor (HT) arises from disruption of the cerebellothalamocortical pathways. A lesion can interrupt the projection at any point, resulting in this tremor. We describe a case of HT due to the rare artery of Percheron infarct and its successful treatment using deep brain stimulation. Case report: A 62-year-old woman with a right medial cerebral peduncle and bilateral thalamic stroke developed HT. Ventral intermediate nucleus (Vim) zona incerta (ZI) deep brain stimulation (DBS) surgery was performed, with improvement in her tremor. Discussion: Our case supports the theory that the more caudal ZI target in combination with Vim is beneficial in treating poorly DBS-responsive tremors such as HT.

To investigate changes in tremor severity over repeated spiral drawings to assess whether learning deficits can be evaluated directly in a limb in essential tremor (ET). A motor learning deficit in ET, possibly mediated by cerebellar pathways, has been established in eye-blink conditioning studies, but not paradigms measuring from an affected, tremulous limb. Computerized spiral analysis captures multiple characteristics of Archimedean spirals and quantifies performance through calculated indices. Sequential spiral drawing has recently been suggested to demonstrate improvement across trials among ET subjects. One hundred and sixty-one ET and 80 age-matched control subjects drew 10 consecutive spirals on a digitizing tablet. Degree of severity (DoS), a weighted, computational score of spiral execution that takes into account spiral shape and line smoothness, previously validated against a clinical rating scale, was calculated in both groups. Tremor amplitude (Ampl), an independent index of tremor size, measured in centimeters, was also calculated. Changes in DoS and Ampl across trials were assessed using linear regression with slope evaluations. Both groups demonstrated improvement in DoS across trials, but with less improvement in the ET group compared to controls. Ampl demonstrated a tendency to worsen across trials in ET subjects. ET subjects demonstrated less improvement than controls when drawing sequential spirals, suggesting a possible motor learning deficit in ET, here captured in an affected limb. DoS improved independently of Ampl, showing that DoS and Ampl are separable motor physiologic components in ET that may be independently mediated.

Objective: To identify pre-operative clinical and computerized spiral analysis characteristics that may help ascertain which patients with Essential Tremor (ET) will exhibit 'early tolerance' to ventral intermediate nucleus of thalamus (Vim) deep brain stimulation (DBS). Methods: Identification of comparative characteristics of defined cases of 'early tolerance' versus patients with sustained satisfactory response treated with Vim DBS surgery for medically-refractory ET, based on retrospective chart review by a clinician blinded to the findings of computerized spiral analysis. Results: Statistically significant differences in two spiral analysis indices, SWVI and DoS, were found in the dominant upper limbs of patients who developed 'early tolerance', whereas the clinical characteristics were not significantly different. Conclusion: Objective measurements of upper limb kinematics using graphonomic tests like spiral analysis should be considered in the pre-operative evaluation for DBS, especially in the setting of moderate-severe predominantly action and proximal postural tremors. Significance: Ours is the first investigation looking into the pre-operative clinical and objective physiologic characteristics of the patients who develop 'early tolerance' to Vim DBS for the treatment of essential tremor. The study has significant implications for pre-operative evaluation and potential surgical target selection for the treatment of tremors. Published by Elsevier B.V. on behalf of International Federation of Clinical Neurophysiology.

BACKGROUND:Many different oligosynaptic reflexes are known to originate in the lower brainstem which share phenomenological and neurophysiological similarities.OBJECTIVE:To evaluate and discuss the differences and aberrancies among these reflexes, which are hard to discern clinically using neurophysiological investigations with the help of a case report.METHODS:We describe the clinical and neurophysiological assessment of a young man who had a childhood history of opsoclonus-myoclonus syndrome with residual mild ataxia and myoclonic jerks in the distal extremities presenting with subacute onset total body jerks sensitive to sound and touch (in a limited dermatomal distribution), refractory to medications.RESULTS:Based on clinical characteristics and insights gained from neurophysiological testing we could identify a novel reflex of caudal brainstem origin.CONCLUSIONS:The reflex described is likely an exaggerated normal reflex, likely triggered by a dolichoectatic vertebral arterial compression and shares characteristics of different reflexes known to originate in caudal brainstem, which subserve distinctive roles in human postural control.

Introduction: Objective measures for detection and quantification of dystonic movements may guide both diagnosis and clinical monitoring. Digitized spiral analysis is a non-invasive method used to assess upper limb motor control in movement disorders and may have utility in dystonia. We aimed to determine if digitized spiral analysis can distinguish dystonia subjects from controls, and evaluated correlation with a validated clinical rating scale. Methods: Kinematic, dynamic, and spatial attributes of Archimedean spirals drawn with an inking pen on a digitizing tablet were compared for participants with brachial dystonia and either Tor1A (DYT1) (n = 15) or THAP1 (DYT6) mutations (n = 12) and age and gender matched controls (n = 27) using Receiver Operator Characteristics (ROC) analysis. Spiral indices including an overall degree of severity (DoS) were also calculated and correlated with clinical severity ratings as measured by the Burke-Fahn-Marsden scale. Results: Dystonia spirals had significantly higher severity scores as well as higher measures of spiral irregularity compared to controls. ROC analysis demonstrated that the DoS score had good discriminative ability to distinguish dystonia spirals from controls, with an Area Under the Curve (AUC) of 0.87. Measures of spiral irregularity correlated with validated clinical rates of dystonia severity in the analyzed arm, with one particular index, Residue of Theta vs R, showing the highest correlation (r = 0.55, p = 0.005). Conclusion: Digitized spiral analysis may be a promising non-invasive method to objectively quantify brachial dystonia. It may also be a useful way to monitor subtle changes in dystonia severity over time not captured with current clinical rating scales.

Background: Mild and transient head tremor may sometimes be observed in otherwise tremor-free relatives of essential tremor (ET) cases, although its prevalence is unclear A diagnostic question is whether this transient, isolated head tremor, often observed as no more than a wobble, is an early manifestation of ET or whether it is a normal finding. A direct comparison with controls is needed. Methods: Two hundred and forty-one first-degree relatives of ET cases (FD-ET) and 77 spousal controls (Co) were enrolled in a study of ET. Each underwent a detailed evaluation that included a tremor history and videotaped neurological examination. None of the enrollees reported tremor, had a prior diagnosis of ET, or had significant tremor on screening spirals. All videotaped examinations were initially reviewed by a movement disorder neurologist blinded to subject type, and among those with head tremor on examination, co-reviewed by two additional movement disorders neurologists. Results: Twenty-six (10.8, 95% Confidence interval [CI] = 7.5-15.3%) of 241 FD-ET vs. 2 (2.6, 95% CI = 0.7-9.0%) of 77 Co had isolated, transient head tremor (odds ratio = 4.54, 95% CI = 1.05-19.57, p = 0.04). No enrollee had significant upper extremity tremor and none met inclusion criteria for ET based on the presence of upper extremity tremor. With one exception, head tremor occurred during or after phonation. It was always transient (generally a single back and forth wobble) and rare (observed briefly on one or two occasions during the videotaped examination) and had a faster frequency, lower amplitude and a different quality than voluntary head shaking. Conclusion: The basis for the observed isolated head tremor is unknown, but it could be an early feature of ET in ET families. Indeed, one-in-ten otherwise unaffected first-degree relatives of ET cases exhibited such tremor. To a far lesser extent it was also observed in "unaffected" controls. In both, it is likely a sign of early, emerging, undiagnosed ET, although follow-up studies are needed to confirm this. If it were ET, it would indicate that the prevalence of ET may be considerably higher than previously suspected.

Objective: To investigate whether repeated spiral drawings distinguish motor learning from changes in tremor amplitude. Background: Computerized spiral analysis captures kinematic, dynamic, and spatial attributes of Archimedean spirals and calculates several indices to quantify disability and assess motor performance. Subjects with essential tremor (ET) show improved performance over repeated spiral drawings but it is unclear whether this is due to reduction in tremor amplitude or to motor learning. Methods: 170 ET (mean age 83.7±5.9 years) and 30 healthy (83.1±3.0 years) subjects freely drew ten spirals with each hand on a digitizing tablet. Drawing severity, incorporating curve smoothness, shape deviations, and tremor amplitude were measured. Amplitude calculations were not used in the severity index. Severity improvement was a measure of motor learning. Changes in severity and amplitude were assessed using slope evaluations, repeated measures, and post-hoc analyses. Results: 3,289 spirals from ET and 274 from controls were evaluated. Severity was greater in ET vs controls (2.95±0.94 vs 1.05±0.50, p<.001), which was maintained from the first trial (3.1±0.05 vs 1.33±0.10, p<.001) to the tenth trial (2.87±0.05 vs 1.01±0.13, p<.001). Pairwise evaluations showed that improvement in severity did not change after trial 4 in subjects who improved; however, fewer ET compared to controls (64[percnt] vs 77[percnt]) decreased their severity scores (p<0.05). In ET subjects, tremor amplitude (mean 7.33±9.3, range 0-90.1 mm) did not differ from trials 1-10 (7.0±8.4 mm vs 7.9±1.01 mm), with an equal tendency to increase or decrease regardless of change in severity. Conclusions: Repeated spiral drawings in ET subjects showed improvements due to quantifiable changes in drawing severity, unrelated to tremor amplitudes. These findings highlight the differences between motor learning and involuntary tremor movements. They also imply that ET subjects may exhibit deficits in motor learning compared to controls, possibly mediated by cerebellar circuitry thought to abnormal in ET.

Objective:To characterize brachial dystonia in DYT1 and DYT6 dystonia using digitized Archimedes spiral drawing. Background:Measures for detection and quantification of dystonia are needed. Assessments of drawing and writing present an opportunity to objectively evaluate individuals with brachial dystonia. Digitized spiral analysis is a non-invasive test that has demonstrated discriminative value in Parkinson disease and essential tremor, but is not well described in brachial dystonia. It captures kinematic, dynamic, and spatial attributes of freely drawn Archimedes spirals, and computes a series of spiral indices to quantify motor performance. Methods:27 dystonia patients (mean age: 33yrs; 8-66) with mutations in TOR1A (DYT1)(n=15) or THAP1 (DYT6)(n=12) and 27 controls (mean age 40yrs; 20-66) drew 10 spirals with each hand on a digitizing tablet. Spirals from the affected arm (21 right, 6 left) were compared to 27 controls matched for age and handedness (24 right, 3 left; mean age 40yrs; 20-66). In bi-brachial patients, the dominant arm was analyzed. Results:Dystonia subjects showed worse spiral severity scores compared to controls (1.58 vs 0.59, p<0.0001). Overall pressure was not different (195.0 vs 190.2) but measures of pressure frequency (1.29 vs 0.34, p<0.0001), and power (3.25 vs 0.55, p=0.0002) were greater in dystonic subjects. Measures of spiral irregularity, including spiral smoothness (-3.3 vs -4.8, p=0.001), the residue of radius versus Theta (0.32 vs 0.23, p=0.0002), and width variability (0.388 vs 0.239, p<0.0001) were abnormal. Mean speed did not differ between groups. No differences were found comparing THAP1 to TOR1A. Conclusions:Digitized spirals reveal quantifiable differences in genetic forms of brachial dystonia compared to controls. Overall spiral severity, is worse, measures of spiral shape, pressure frequency and power are abnormal. Further study is warranted to determine how spiral indices correlate with other features of dystonia, or help discriminate dystonia from other movement disorders.

Background: Digital analysis of writing and drawing has become a valuable research and clinical tool for the study of upper limb motor dysfunction in patients with essential tremor, Parkinson's disease, dystonia, and related disorders. We developed a validated method of computerized spiral analysis of hand-drawn Archimedean spirals that provides insight into movement dynamics beyond subjective visual assessment using a Wacom graphics tablet. While the Wacom tablet method provides robust data, more widely available mobile technology platforms exist.New method: We introduce a novel adaptation of the Wacom-based method for the collection of hand drawn kinematic data using an Apple iPad. This iPad-based system is stand-alone, easy-to-use, can capture drawing data with either a finger or capacitive stylus, is precise, and potentially ubiquitous.Results: The iPad-based system acquires position and time data that is fully compatible with our original spiral analysis program. All of the important indices including degree of severity, speed, presence of tremor, tremor amplitude, tremor frequency, variability of pressure, and tightness are calculated from the digital spiral data, which the application is able to transmit.Comparison with existing method: While the iPad method is limited by current touch screen technology, it does collect data with acceptable congruence compared to the current Wacom-based method while providing the advantages of accessibility and ease of use.Conclusions: The iPad is capable of capturing precise digital spiral data for analysis of motor dysfunction while also providing a convenient, easy-to-use modality in clinics and potentially at home. (C) 2016 Elsevier B.V. All rights reserved.