Temporomandibular disorder-related characteristics and treatment outcomes in Oromandibular Dystonia patients in two different clinical settings: A cross-sectional study.

INTRODUCTION: Clinical presentation of oromandibular dystonia (OMD) is variable that can be further complicated by the presence of temporomandibular disorder (TMD) symptoms. We sought to evaluate variations in the clinical presentation of OMD patients, particularly TMD-related characteristics, in two clinical settings. METHODS: In a cross-sectional study design, a Web-based data collection survey was provided to eligible patients with OMD from movement disorder (MD) and oro-facial pain (OFP) clinics. The survey questionnaire was designed to collect information on demographic characteristics, clinical presentation particularly related to TMD, quality of life and treatment outcomes. Validated questionnaires were used when available such as the TMD Pain Screener, EuroQol 5-Dimensions 5-Levels (EQ-5D-5L), Jaw Functional Limitation Scale and Global Rating of Change Scale. RESULTS: Of 53 eligible patients, 31 responded to the survey for a 58% response rate. Forty-eight per cent of patients in the MD clinic and 60% of patients in the OFP clinic reported jaw pain along with involuntary movements. Of those, 90% from the MD group and 83% from the OFP group screened positive with the TMD Pain Screener at the onset of symptoms based on recall. Positive TMD Pain Screener response was observed in about 40% of patients in both clinics within 30 days of questionnaire response. No statistically significant differences were observed between two groups for any measured variables. CONCLUSION: Patients with OMD have features of TMD, irrespective of the clinical setting in which they seek and receive care. OMD patients from both clinics were similar in terms of clinical presentation, quality of life and treatment outcomes.

Clinical features and autonomic testing predict survival in multiple system atrophy.

Multiple system atrophy is characterized by autonomic failure along with motor symptoms of parkinsonism and/or cerebellar ataxia. There are differing reports on the influence of certain clinical features, including motor subtype (multiple system atrophy-parkinsonism versus multiple system atrophy-cerebellar ataxia), age of onset, gender, and early autonomic symptoms, on the survival in patients with multiple system atrophy. We sought to evaluate overall survival and predictors of survival in a large cohort of patients with multiple system atrophy seen at a single referral centre where objective autonomic testing is routinely performed for this indication. All cases of multiple system atrophy evaluated at Mayo Clinic, Rochester and assessed with an autonomic reflex screen between January 1998 and December 2012 were retrospectively reviewed. A total of 685 patients were identified; 594 met criteria for probable multiple system atrophy, and 91 for possible multiple system atrophy. Multiple system atrophy-parkinsonism was the predominant subtype in 430 patients (63%). Average age of onset was earlier in multiple system atrophy-cerebellar ataxia (58.4 years) compared to multiple system atrophy-parkinsonism (62.3 years; P < 0.001). Median disease duration from symptom onset to death was 7.51 years (95% confidence interval 7.18-7.78) while time from diagnosis to death was 3.33 years (95% confidence interval 2.92-3.59). There was no difference in survival between motor subtypes of multiple system atrophy (P = 0.232). An initial motor symptom was most common (61%) followed by autonomic onset (28%) and combined motor and autonomic symptoms (11%). The initial onset of either motor or autonomic symptoms did not influence length of survival. However, a number of clinical and autonomic laboratory features predicted unfavourable survival in a univariate analysis. A multivariate model retained the following unfavourable predictors of survival: (i) falls within 3 years of onset (hazard ratio 2.31, P < 0.0001); (ii) bladder symptoms (hazard ratio 1.96, P < 0.0001); (iii) urinary catheterization within 3 years of symptom onset (hazard ratio 1.67, P < 0.003); (iv) orthostatic intolerance within 1 year of symptom onset (hazard ratio 1.28, P < 0.014); (v) older age of onset (hazard ratio 1.02, P = 0.001); and (vi) degree of autonomic failure as measured by a validated composite autonomic severity score (hazard ratio 1.07, P < 0.0023). We conclude that carefully selected clinical features can be used to predict survival in patients with multiple system atrophy. Autonomic testing adds an additional, independent predictor of survival, demonstrating its value not only in the diagnosis of multiple system atrophy but also as prognostic marker.

Stimulation-Induced Transient Nonmotor Psychiatric Symptoms following Subthalamic Deep Brain Stimulation in Patients with Parkinson's Disease: Association with Clinical Outcomes and Neuroanatomical Correlates.

BACKGROUND: The clinical and neurobiological underpinnings of transient nonmotor (TNM) psychiatric symptoms during the optimization of stimulation parameters in the course of subthalamic nucleus deep brain stimulation (STN-DBS) remain under intense investigation. METHODS: Forty-nine patients with refractory Parkinson's disease underwent bilateral STN-DBS implants and were enrolled in a 24-week prospective, naturalistic follow-up study. Patients who exhibited TNM psychiatric manifestations during DBS parameter optimization were evaluated for potential associations with clinical outcome measures. RESULTS: Twenty-nine TNM+ episodes were reported by 15 patients. No differences between TNM+ and TNM- groups were found in motor outcome. However, unlike the TNM- group, TNM+ patients did not report improvement in subsyndromal depression or quality of life. TNM+ episodes were more likely to emerge during bilateral monopolar stimulation of the medial STN. CONCLUSIONS: The occurrence of TNM psychiatric symptoms during optimization of stimulation parameters was associated with the persistence of subsyndromal depression and with lower quality of life ratings at 6 months. The neurobiological underpinnings of TNM symptoms are investigated yet remain difficult to explain.

High frequency oscillations are associated with cognitive processing in human recognition memory.

High frequency oscillations are associated with normal brain function, but also increasingly recognized as potential biomarkers of the epileptogenic brain. Their role in human cognition has been predominantly studied in classical gamma frequencies (30-100 Hz), which reflect neuronal network coordination involved in attention, learning and memory. Invasive brain recordings in animals and humans demonstrate that physiological oscillations extend beyond the gamma frequency range, but their function in human cognitive processing has not been fully elucidated. Here we investigate high frequency oscillations spanning the high gamma (50-125 Hz), ripple (125-250 Hz) and fast ripple (250-500 Hz) frequency bands using intracranial recordings from 12 patients (five males and seven females, age 21-63 years) during memory encoding and recall of a series of affectively charged images. Presentation of the images induced high frequency oscillations in all three studied bands within the primary visual, limbic and higher order cortical regions in a sequence consistent with the visual processing stream. These induced oscillations were detected on individual electrodes localized in the amygdala, hippocampus and specific neocortical areas, revealing discrete oscillations of characteristic frequency, duration and latency from image presentation. Memory encoding and recall significantly modulated the number of induced high gamma, ripple and fast ripple detections in the studied structures, which was greater in the primary sensory areas during the encoding (Wilcoxon rank sum test, P = 0.002) and in the higher-order cortical association areas during the recall (Wilcoxon rank sum test, P = 0.001) of memorized images. Furthermore, the induced high gamma, ripple and fast ripple responses discriminated the encoded and the affectively charged images. In summary, our results show that high frequency oscillations, spanning a wide range of frequencies, are associated with memory processing and generated along distributed cortical and limbic brain regions. These findings support an important role for fast network synchronization in human cognition and extend our understanding of normal physiological brain activity during memory processing.

Network oscillations modulate interictal epileptiform spike rate during human memory.

Eleven patients being evaluated with intracranial electroencephalography for medically resistant temporal lobe epilepsy participated in a visual recognition memory task. Interictal epileptiform spikes were manually marked and their rate of occurrence compared between baseline and three 2 s periods spanning a 6 s viewing period. During successful, but not unsuccessful, encoding of the images there was a significant reduction in interictal epileptiform spike rate in the amygdala, hippocampus, and temporal cortex. During the earliest encoding period (0-2000 ms after image presentation) in these trials there was a widespread decrease in the power of theta, alpha and beta band local field potential oscillations that coincided with emergent focal gamma frequency activity. Interictal epileptiform spike rate correlated with spectral band power changes and broadband (4-150 Hz) desynchronization, which predicted significant reduction in interictal epileptiform spike rate. Spike-triggered averaging of the field potential power spectrum detected a burst of low frequency synchronization 200 ms before the interictal epileptiform spikes that arose during this period of encoding. We conclude that interictal epileptiform spikes are modulated by the patterns of network oscillatory activity that accompany human memory offering a new mechanistic insight into the interplay of cognitive processing, local field potential dynamics and interictal epileptiform spike generation.

Mood stability in Parkinson disease following deep brain stimulation: a 6-month prospective follow-up study.

BACKGROUND: Deep brain stimulation for Parkinson disease has been associated with psychiatric adverse effects including anxiety, depression, mania, psychosis, and suicide. OBJECTIVE: The purpose of this study was to evaluate the safety of deep brain stimulation in a large Parkinson disease clinical practice. METHODS: Patients approved for surgery by the Mayo Clinic deep brain stimulation clinical committee participated in a 6-month prospective naturalistic follow-up study. In addition to the Unified Parkinson's Disease Rating Scale, stability and psychiatric safety were measured using the Beck Depression Inventory, Hamilton Depression Rating Scale, and Young Mania Rating scale. Outcomes were compared in patients with Parkinson disease who had a psychiatric history to those with no co-morbid psychiatric history. RESULTS: The study was completed by 49 of 54 patients. Statistically significant 6-month baseline to end-point improvement was found in motor and mood scales. No significant differences were found in psychiatric outcomes based on the presence or absence of psychiatric comorbidity. CONCLUSIONS: Our study suggests that patients with Parkinson disease who have a history of psychiatric co-morbidity can safely respond to deep brain stimulation with no greater risk of psychiatric adverse effect occurrence. A multidisciplinary team approach, including careful psychiatric screening ensuring mood stabilization and psychiatric follow-up, should be viewed as standard of care to optimize the psychiatric outcome in the course of deep brain stimulation treatment.

Pathological and physiological high-frequency oscillations in focal human epilepsy.

High-frequency oscillations (HFO; gamma: 40-100 Hz, ripples: 100-200 Hz, and fast ripples: 250-500 Hz) have been widely studied in health and disease. These phenomena may serve as biomarkers for epileptic brain; however, a means of differentiating between pathological and normal physiological HFO is essential. We categorized task-induced physiological HFO during periods of HFO induced by a visual or motor task by measuring frequency, duration, and spectral amplitude of each event in single trial time-frequency spectra and compared them to pathological HFO similarly measured. Pathological HFO had higher mean spectral amplitude, longer mean duration, and lower mean frequency than physiological-induced HFO. In individual patients, support vector machine analysis correctly classified pathological HFO with sensitivities ranging from 70-98% and specificities >90% in all but one patient. In this patient, infrequent high-amplitude HFO were observed in the motor cortex just before movement onset in the motor task. This finding raises the possibility that in epileptic brain physiological-induced gamma can assume higher spectral amplitudes similar to those seen in pathologic HFO. This method if automated and validated could provide a step towards differentiating physiological HFO from pathological HFO and improving localization of epileptogenic brain.

Lateral cerebellothalamic tract activation underlies DBS therapy for Essential Tremor.

BACKGROUND: While deep brain stimulation (DBS) therapy can be effective at suppressing tremor in individuals with medication-refractory Essential Tremor, patient outcome variability remains a significant challenge across centers. Proximity of active electrodes to the cerebellothalamic tract (CTT) is likely important in suppressing tremor, but how tremor control and side effects relate to targeting parcellations within the CTT and other pathways in and around the ventral intermediate (VIM) nucleus of thalamus remain unclear. METHODS: Using ultra-high field (7T) MRI, we developed high-dimensional, subject-specific pathway activation models for 23 directional DBS leads. Modeled pathway activations were compared with post-hoc analysis of clinician-optimized DBS settings, paresthesia thresholds, and dysarthria thresholds. Mixed-effect models were utilized to determine how the six parcellated regions of the CTT and how six other pathways in and around the VIM contributed to tremor suppression and induction of side effects. RESULTS: The lateral portion of the CTT had the highest activation at clinical settings (p < 0.05) and a significant effect on tremor suppression (p < 0.001). Activation of the medial lemniscus and posterior-medial CTT was significantly associated with severity of paresthesias (p < 0.001). Activation of the anterior-medial CTT had a significant association with dysarthria (p < 0.05). CONCLUSIONS: This study provides a detailed understanding of the fiber pathways responsible for therapy and side effects of DBS for Essential Tremor, and suggests a model-based programming approach will enable more selective activation of lateral fibers within the CTT.

Autopsy confirmed multiple system atrophy cases: Mayo experience and role of autonomic function tests.

BACKGROUND: Multiple system atrophy (MSA) is a sporadic progressive neurodegenerative disorder characterised by autonomic failure, manifested as orthostatic hypotension or urogenital dysfunction, with combinations of parkinsonism that is poorly responsive to levodopa, cerebellar ataxia and corticospinal dysfunction. Published autopsy confirmed cases have provided reasonable neurological characterisation but have lacked adequate autonomic function testing. OBJECTIVES: To retrospectively evaluate if the autonomic characterisation of MSA is accurate in autopsy confirmed MSA and if consensus criteria are validated by autopsy confirmation. METHODS: 29 autopsy confirmed cases of MSA evaluated at the Mayo Clinic who had undergone formalised autonomic testing, including adrenergic, sudomotor and cardiovagal functions and Thermoregulatory Sweat Test (TST), from which the Composite Autonomic Severity Score (CASS) was derived, were included in the study. PATIENT CHARACTERISTICS: 17 men, 12 women; age of onset 57±8.1 years; disease duration to death 6.5±3.3 years; first symptom autonomic in 18, parkinsonism in seven and cerebellar in two. Clinical phenotype at first visit was MSA-P (predominant parkinsonism) in 18, MSA-C (predominant cerebellar involvement) in eight, pure autonomic failure in two and Parkinson's disease in one. Clinical diagnosis at last visit was MSA for 28 cases. Autonomic failure was severe: CASS was 7.2±2.3 (maximum 10). TST% was 65.6±33.9% and exceeded 30% in 82% of patients. The most common pattern was global anhidrosis. Norepinephrine was normal supine (203.6±112.7) but orthostatic increment of 33.5±23.2% was reduced. Four clinical features (rapid progression, early postural instability, poor levodopa responsiveness and symmetric involvement) were common. CONCLUSION: The pattern of severe and progressive generalised autonomic failure with severe adrenergic and sudomotor failure combined with the clinical phenotype is highly predictive of MSA.

Underlying neurobiology and clinical correlates of mania status after subthalamic nucleus deep brain stimulation in Parkinson's disease: a review of the literature.

Deep brain stimulation (DBS) is a novel and effective surgical intervention for refractory Parkinson's disease (PD). The authors review the current literature to identify the clinical correlates associated with subthalamic nucleus (STN) DBS-induced hypomania/mania in PD patients. Ventromedial electrode placement has been most consistently implicated in the induction of STN DBS-induced mania. There is some evidence of symptom amelioration when electrode placement is switched to a more dorsolateral contact. Additional clinical correlates may include unipolar stimulation, higher voltage (>3 V), male sex, and/or early-onset PD. STN DBS-induced psychiatric adverse events emphasize the need for comprehensive psychiatric presurgical evaluation and follow-up in PD patients. Animal studies and prospective clinical research, combined with advanced neuroimaging techniques, are needed to identify clinical correlates and underlying neurobiological mechanisms of STN DBS-induced mania. Such working models would serve to further our understanding of the neurobiological underpinnings of mania and contribute valuable new insight toward development of future DBS mood-stabilization therapies.

Utility of tremor electrophysiology studies.

OBJECTIVE: To determine the utility of tremor electrophysiology testing in differentiating clinically indeterminate tremor due to organic, functional, and mixed tremor types. BACKGROUND: Prior studies have shown that electrophysiological studies increase diagnostic sensitivity of tremor syndromes; however, few have examined mixed organic and functional tremors. METHODS: Patients referred for tremor to the Mayo Clinic, Rochester movement disorders lab were consecutively selected and retrospectively reviewed. Surface electromyography (EMG) recordings of upper limb muscles were performed at rest, posture, with action and distractibility tasks. RESULTS: Of 116 patients, all were clinically described as having either a resting tremor, postural tremor, action tremor, postural and action tremor, mixed resting, postural, and action tremor, or nonspecific tremulousness. Based on electrophysiological features, patients were diagnosed with organic tremor (parkinsonian, essential, mixed, rubral, cerebellar, non-specific tremulousness), functional tremor, or mixed functional and organic tremors. The median disease duration at electrophysiological confirmation of diagnosis was shorter for functional tremor at 1.5 years (IQR 1-9.3), and organic tremor at 3 years (IQR 1-15), versus mixed organic and functional tremor at 11 years (IQR 2-15) (p = 0.0422). The electrophysiology study clarified the referral/clinical diagnosis in 87 patients (75%), 26 (29.5%) of whom had functional tremor, and 61 (70.1%) had organic tremor or mixed organic/functional tremor. Variability of tremor during electrophysiology testing was associated with a change in diagnosis (p = 0.0286). CONCLUSION: Our findings show that electrophysiological assessment of tremor can be helpful in the clinical diagnosis of patients with both organic and functional tremor.

PSP-like syndrome after aortic surgery in adults (Mokri syndrome).

BACKGROUND: A rare progressive supranuclear palsy-like syndrome seemingly triggered by aortic surgery was first described in 2004. This largest case series to date describes the features of this syndrome. METHODS: We searched the Mayo Clinic electronic medical records using the advanced cohort explorer search engine for patients evaluated for neurologic symptoms after cardiac-aortic surgery in the past 30 years. Data were extracted to Microsoft Excel from the identified patients and included clinical and neuroimaging features and outcomes. RESULTS: Twenty-five patients met the inclusion criteria. All surgeries were performed under thoracic aortic bypass and deep hypothermia. Surgery included aortic aneurysm, aortic valve repair, and/or aortic dissection repair. Surgical records were unavailable, although surgery was documented in the Mayo record as uncomplicated in 60% of cases. In the remaining cases, no particular intraoperative or postoperative complications were documented at a high frequency. A typical triad was documented: supranuclear gaze palsy (SNGP; 100%), gait imbalance (80%), and dysarthria (96%). Part or all of the triad was observed before hospital discharge and stabilized over the course of days-weeks. A second phase of symptom worsening plus new symptoms developed up to a year later; this decline continued for up to several years before stabilization. Delayed epileptic seizures occurred in 32% of patients. Brain MRI revealed only nonspecific findings. CONCLUSION: This syndrome following adult thoracic aortic bypass surgery with deep hypothermia remains unexplained. It follows a biphasic course and is characterized by the triad of SNGP, unsteady gait, and a predominantly ataxic dysarthria.

Psychogenic tremor: long-term prognosis in patients with electrophysiologically confirmed disease.

We describe the presenting features and long-term outcomes of patients with electrophysiologically-confirmed psychogenic tremor. Clinical information for all patients with psychogenic tremor confirmed by our Movement Disorders Neurophysiology Laboratory (2003-2004) was reviewed. A follow-up questionnaire was administered to all included patients in 2007. Psychogenic tremor was documented in 62 patients; 33 responded to the questionnaire (53%). Median onset-age was 50 years (range, 15-71); 23 were female (70%). Clinical certainty of psychogenic etiology was: definite, 8 (24%); probable, 16 (49%), and possible, 9 (27%). Characteristic electrodiagnostic features of psychogenic tremor were documented in all. All but two patients were ultimately given a definite diagnosis of psychogenic tremor; recommended psychiatric consultation was only done by 12 (36%). Twenty-one patients (64%) rated tremor disability as moderate or severe after a median follow-up of 5.1 years (range, 3.3-19). Improvement occurred spontaneously in 5 (15%), and after a specific intervention in 4 (12%), whereas 3 (9%) had mild but unchanged symptoms. The mean duration of symptoms, prior to diagnosis with psychogenic tremor, was significantly shorter for patients with mild or no tremor at follow-up (P = 0.037). Physiologically-confirmed psychogenic tremor carries a poor prognosis, with unremitting or worse tremor persisting 3-years after diagnosis in most.

Conjugal multiple system atrophy: Chance, shared risk factors, or evidence of transmissibility?

OBJECTIVE: To describe conjugal multiple system atrophy (MSA) in a couple married for 44 years, and to report environmental risk factors possibly contributing to the occurrence. METHODS: Case description of conjugal MSA with report of shared environmental risk factors and retrospective review of consecutively diagnosed MSA patients between 1998 and 2012 with autonomic reflex screen at Mayo Clinic, Rochester (clinical series). Probability calculation was based on the age-specific point prevalence of MSA. RESULTS: A husband and wife both developed MSA symptoms at age 63. The husband's onset was of imbalance, followed by falls and genitourinary failure; parkinsonism and antecollis was evident on examination. Autonomic testing showed widespread autonomic failure. The patient died 2.25 years after onset. The wife initially developed urinary symptoms progressing to incontinence. Parkinsonism, dysphonia, and falls began within 1 year. Autonomic testing revealed severe autonomic failure. Interview with the surviving wife and son revealed substantial chemical exposure, in particular pesticides. In our clinical series, there were no other cases of conjugal MSA. Assuming an age-specific point prevalence of MSA based on population studies and independence of the two events, the probability of both individuals developing MSA by chance is 6.08 e-9. CONCLUSION: Based on the population point prevalence of MSA, conjugal MSA is rare but possible. We conclude that this case of conjugal MSA likely occurred by chance; however, exposure to shared risk factors (pesticides) may be contributory. Because this is the first reported case of conjugal MSA, to our best knowledge, evidence for transmissibility between spouses is lacking.

Intrathecal administration of autologous mesenchymal stem cells in multiple system atrophy.

OBJECTIVE: This phase I/II study sought to explore intrathecal administration of mesenchymal stem cells (MSCs) as therapeutic approach to multiple system atrophy (MSA). METHODS: Utilizing a dose-escalation design, we delivered between 10 and 200 million adipose-derived autologous MSCs intrathecally to patients with early MSA. Patients were closely followed with clinical, laboratory, and imaging surveillance. Primary endpoints were frequency and type of adverse events; key secondary endpoint was the rate of disease progression assessed by the Unified MSA Rating Scale (UMSARS). RESULTS: Twenty-four patients received treatment. There were no attributable serious adverse events, and injections were generally well-tolerated. At the highest dose tier, 3 of 4 patients developed low back/posterior leg pain, associated with thickening/enhancement of lumbar nerve roots. Although there were no associated neurologic deficits, we decided that dose-limiting toxicity was reached. A total of 6 of 12 patients in the medium dose tier developed similar, but milder and transient discomfort. Rate of progression (UMSARS total) was markedly lower compared to a matched historical control group (0.40 ± 0.59 vs 1.44 ± 1.42 points/month, p = 0.004) with an apparent dose-dependent effect. CONCLUSIONS: Intrathecal MSC administration in MSA is safe and well-tolerated but can be associated with a painful implantation response at high doses. Compelling dose-dependent efficacy signals are the basis for a planned placebo-controlled trial. CLASSIFICATION OF EVIDENCE: This phase I/II study provides Class IV evidence that for patients with early MSA, intrathecal MSC administration is safe, may result in a painful implantation response at high doses, and is associated with dose-dependent efficacy signals.

The spectrum of disorders presenting as adult-onset focal lower extremity dystonia.

BACKGROUND: Uncommonly, adult-onset dystonia is confined to one lower extremity. We sought to characterize the clinical spectrum associated with the presenting phenotype of lower limb dystonia including foot torsion. METHODS: Retrospective computer search of the Mayo Clinic Medical Records Linkage System (1996-2006). Inclusion criteria were (1) a principal, initial diagnosis of monomelic lower extremity dystonia with foot torsion; (2) no neurologic findings outside of the affected limb; (3) age-onset>18 years. Prospective data were sought from apparent idiopathic cases. RESULTS: We identified 36 patients (31 females) presenting with monomelic lower limb dystonia including foot torsion. Onset was usually subacute or insidious (32 patients); mean symptom duration was 28.8 months (range, 1-96), age-onset 47.5 years (range, 21-77). After a mean follow-up of 3.1 years, causes were identified in over half, including 5 with parkinsonism. Other treatable etiologies included psychogenic dystonia (3 patients) and stiff-limb syndrome (2 patients). Post-traumatic dystonia was diagnosed in 10 patients and consistently manifested as fixed, painful foot torsion, in contrast to the action-induced dystonia in 5 parkinsonism cases, and 10 of 14 patients with primary lower limb dystonia. Imaging identified the cause in only 1 patient (ischemic stroke) and was negative in the single patient with pyramidal signs. CONCLUSIONS: Adults presenting with monomelic lower limb dystonia with foot torsion often have an identifiable cause, sometimes treatable, including Parkinson's disease (diagnosed with levodopa trial) or immune-mediated stiff-limb syndrome. Post-traumatic dystonia was the single most frequent cause and proved difficult to treat. Unlike certain other series of such patients, psychogenic dystonia was an uncommon clinical diagnosis.

Camptocormia: Etiology, diagnosis, and treatment response.

BACKGROUND: We sought to determine the etiologies, diagnostic testing, and management of a retrospective cohort of patients with camptocormia evaluated at a single center. METHODS: We reviewed medical records of all adult patients evaluated at Mayo Clinic Rochester with a diagnosis of camptocormia from 2000 to 2014. Demographic and clinical data were abstracted and analyzed. RESULTS: There were 276 patients (58.0% male), with mean age at presentation of 68.6 (±12.7) years. An etiology was identified in 98.2%. The most common etiologies were idiopathic Parkinson disease (22.5%), idiopathic axial myopathy (14.1%), and degenerative joint disease without fixed deformity (13.0%). We also identified several rare causes of camptocormia. Investigations included spine imaging, needle and surface EMG, and muscle biopsy. Most patients received physical therapy and orthotic support with limited benefit. Limited improvement of camptocormia was seen where a treatable etiology was identified. CONCLUSIONS: An etiology can be identified in almost all cases of camptocormia. Most cases are due to 3 common disorders: Parkinson disease, axial myopathy, and degenerative joint disease. A diagnostic and treatment algorithm is proposed.

Glycine receptor modulating antibody predicting treatable stiff-person spectrum disorders.

BACKGROUND: Glycine receptor alpha-1 subunit (GlyRα1)-immunoglobulin G (IgG) is diagnostic of stiff-person syndrome (SPS) spectrum but has been reported detectable in other neurologic diseases for which significance is less certain. METHODS: To assess GlyRα1-IgGs as biomarkers of SPS spectrum among patients and controls, specimens were tested using cell-based assays (binding [4°C] and modulating [antigen endocytosing, 37°C]). Medical records of seropositive patients were reviewed. RESULTS: GlyRα1-IgG (binding antibody) was detected in 21 of 247 patients with suspected SPS spectrum (8.5%) and in 8 of 190 healthy subject sera (4%) but not CSF. Among 21 seropositive patients, 20 had confirmed SPS spectrum clinically, but 1 was later determined to have a functional neurologic disorder. Sera from 9 patients with SPS spectrum , but not 7 controls, nor the functional patient, caused GlyRα1 modulation (100% specificity). SPS spectrum phenotypes included progressive encephalomyelitis with rigidity and myoclonus (PERM) (8), classic SPS (5), stiff limb (5), stiff trunk (1), and isolated exaggerated startle (hyperekplexia, 1). Neuropsychiatric symptoms present in 12 patients (60%) were anxiety (11), depression (6), and delirium (3). Anxiety was particularly severe in 3 patients with PERM. Objective improvements in SPS neurologic symptoms were recorded in 16 of 18 patients who received first-line immunotherapy (89%, 9/10 treated with corticosteroids, 8/10 treated with IVIg, 3/4 treated with plasma exchange, and 1 treated with rituximab). Treatment-sparing maintenance strategies were successful in 4 of 7 patients (rituximab [2/3], azathioprine [1/1], and mycophenolate [1/3]). CONCLUSIONS: GlyRα1-modulating antibody improves diagnostic specificity for immunologically treatable SPS spectrum disorders. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that GlyRα1-modulating antibody accurately identifies patients with treatable SPS spectrum disorders.

Tremor amplitude is logarithmically related to 4- and 5-point tremor rating scales.

Tremor rating scales (TRSs) are used commonly in the clinical assessment of tremor, but the relationship of a TRS to actual tremor amplitude has never been quantified. Consequently, the resolution of these scales is unknown, and the clinical significance of a 1-point change in TRS is uncertain. We therefore sought to determine the change in tremor amplitude that corresponds to a 1-point change in a typical 5-point TRS. Data from five laboratories were analysed, and 928 patients with various types of hand tremor were studied. Hand tremor was quantified with a graphics tablet in three different labs, an accelerometer in three labs and a mechanical-linkage device in one lab. Tremor in writing, drawing, horizontal posture, rest and finger-nose testing was graded using a variety of TRSs. The relationship between TRS scores and tremor amplitude was computed for each task and laboratory. A logarithmic relationship between a 5-point (0-4) TRS and tremor amplitude (T, measured in centimetres) was found in all five labs, despite widely varying rating scales and transducer methodology. Thus, T2/T1 = 10(alpha(TRS2-TRS1)). The value of alpha ranged from 0.414 to 0.441 for writing, 0.355-0.574 for spiral drawing, 0.441 to 0.488 for rest tremor, 0.266-0.577 for postural tremor and 0.306 for finger-nose testing. For alpha = 0.3, 0.4, 0.5, 0.6 and 0.7, the ratios T2/T1 for a 1-point decrease in TRS are 0.501, 0.398, 0.316, 0.251 and 0.200. Therefore, a 1-point change in TRS represents a substantial change in tremor amplitude. Knowledge of the relationship between TRS and precise measures of tremor is useful in interpreting the clinical significance of changes in TRS produced by disease or therapy.

Orthostatic myoclonus after brain tumor radiation: Insights from two lesional cases.

INTRODUCTION: Orthostatic myoclonus (OM) is a recognized syndrome of gait unsteadiness accompanied by lower limb myoclonus provoked by the assumption of an upright posture. OM typically affects the elderly and is often associated with neurodegenerative disease. We sought to review the clinical and electrophysiologic characteristics of OM due to brain tumor treatment, the first reported lesional cases of this rare disorder. METHODS: The database of the Mayo Clinic Rochester Movement Disorders Laboratory was searched for all patients diagnosed with OM from January 2007 to December 2016. All available clinical, radiographic, and surface electromyographic data were reviewed, and patients with a history of primary or metastatic brain tumor were analyzed. RESULTS: Two patients with OM and brain tumor were identified; both had undergone tumor resection and targeted brain radiation. Both patients complained of unsteadiness while walking and recurrent falls. Tumor pathology (atypical meningioma, gliosarcoma) was centered in the frontal lobe and extended to the supplementary motor area (SMA), pre-SMA, or prefrontal cortex. Medications did not improve gait. CONCLUSION: Two cases of brain tumor-related OM suggest that degeneration of frontal motor programming circuits underlies the pathophysiology of OM.