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.

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.

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.

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.

Precise stimulation location optimizes speech outcomes in essential tremor.

BACKGROUND: Deep brain stimulation for essential arm tremor is often complicated by dysarthria and persistent voice tremor. OBJECTIVE: To determine the relationship of stimulation location to speech outcomes following bilateral thalamic deep brain stimulation (DBS) for essential tremor (ET). METHODS: Eighteen patients undergoing bilateral DBS for ET were prospectively studied. Speech pathologists grouped patients by final speech outcome (normal speech, voice tremor, or dysarthria). Locations of the active leads were calculated by normalizing the segmented thalamic volumes to those in the Morel atlas. Stimulation volumes within thalamic nuclei, error distances from target, and measures of accuracy were calculated and differences in measures between outcome groups tested. RESULTS: At optimal stimulation, 8 patients had normal speech, 6 had voice tremor, and 4 had mild dysarthria. Stimulation volumes were statistically concentrated within the ventral lateral posterior nucleus (VLp). The percentage of stimulation volume outside the VLp was higher in patients with dysarthria (60% vs. 24%, p = 0.02) or voice tremor (55% vs. 24%, p = 0.03) compared to patients with normal speech outcomes. The error distance from the center of VLp was greater for patients with dysarthria than those with normal speech (12.6 vs. 7.6 mm, p = 0.02). Electrodes with lower efficiency for VLp stimulation were more frequent with poor speech outcomes and in patients with persistent voice tremor. CONCLUSIONS: Following bilateral DBS for ET, 22% of patients develop a non-disabling dysarthria. Optimal speech outcomes were achieved in 44% of patients and correlated with precise stimulation location within and not outside of the VLp.

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.

Repetitive exercise dystonia: A difficult to treat hazard of runner and non-runner athletes.

INTRODUCTION: Runner's dystonia has previously been described in small series or case reports as a lower limb, task-specific dystonia. We have occasionally encountered this disorder and recognized the same phenomenon in non-runners regularly engaging in lower limb exercise. We wished to characterize the syndrome further, including outcomes, treatment, and the diagnostic usefulness of electrophysiology. METHODS: We conducted a retrospective review and follow-up survey of adults seen at Mayo Clinic (1996-2015) with task-specific dystonia arising after prolonged repetitive lower limb exercise. The findings were compared to all 21 previously reported cases of runner's dystonia. RESULTS: We identified 20 patients with this condition, 13 runners and seven non-runner athletes. Median age at dystonia onset was in mid-adulthood. Correct diagnosis was delayed by a median of 3.5 years in runners and 1.6 years in non-runners, by which time more than one-third of patients had undergone unsuccessful invasive procedures. Most patients had dystonia onset in the distal lower limb. Dystonia was task-specific with exercise at onset but progressed to affect walking in most. Sensory tricks were reported in some. Surface EMG was consistent with task-specific dystonia in nine patients. Botulinum toxin, levodopa, clonazepam, trihexyphenidyl, and physical therapy provided modest benefit to some, but all patients remained substantially symptomatic at last follow up. CONCLUSIONS: Repetitive exercise dystonia is task-specific, confined to the lower limb and occasionally trunk musculature. It tends to be treatment-refractory and limits ability to exercise. Diagnosis is typically delayed, and unnecessary surgical procedures are common. Surface EMG may aid the diagnosis.

Orthostatic tremor: Clinical, electrophysiologic, and treatment findings in 184 patients.

OBJECTIVE: To evaluate the clinical, electrophysiologic, and treatment outcome features of orthostatic tremor (OT) in a large case series. METHODS: We performed medical record review of 184 patients who met clinical and electrodiagnostic criteria for OT from 1976 to 2013 at the Mayo Clinic. Demographic, clinical, electrophysiologic, and treatment data were extracted. RESULTS: The majority of OT cases were female (63.6%) and mean age at onset was 59.3 years (range 13-85 years). Diagnosis was delayed by a mean of 7.2 years (range 0-44 years). The average tremor frequency was 15.7 Hz (range 12.5-20 Hz), and transmitted to the arms on weight-bearing (95.5%). Patients reported a spectrum of progressive orthostatic leg symptoms, relieved by sitting or leaning. Falls were reported in 24.1%. Coexistent neurologic disorders included essential tremor (22.8%), other tremor (4.9%), and parkinsonism (8.7%). Family history of OT was noted in 4.9%. Of 46 medications trialed, 24 failed to provide any benefit. Benzodiazepines provided at least mild benefit in 55.9%, and moderate to marked benefit in 31.5%; ß-blockers (31.0%) and anticonvulsants (25.0%) provided mild benefit, and the remainder were largely ineffective. Medication benefit waned over time. Deep brain stimulation (DBS) was effective in 2 cases. CONCLUSION: OT predominantly affects female seniors, and the diagnosis should be considered with any orthostatic-induced leg symptoms, and confirmed by surface EMG. Benzodiazepines are the most efficacious treatment, followed by ß-blockers and anticonvulsants. DBS should be further explored for treatment.

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.

Gamma oscillations precede interictal epileptiform spikes in the seizure onset zone.

OBJECTIVE: To investigate the generation, spectral characteristics, and potential clinical significance of brain activity preceding interictal epileptiform spike discharges (IEDs) recorded with intracranial EEG. METHODS: Seventeen adult patients with drug-resistant temporal lobe epilepsy were implanted with intracranial electrodes as part of their evaluation for epilepsy surgery. IEDs detected on clinical macro- and research microelectrodes were analyzed using time-frequency spectral analysis. RESULTS: Gamma frequency oscillations (30-100 Hz) often preceded IEDs in spatially confined brain areas. The gamma-IEDs were consistently observed 35 to 190 milliseconds before the epileptiform spike waveforms on individual macro- and microelectrodes. The gamma oscillations associated with IEDs had longer duration (p < 0.001) and slightly higher frequency (p = 0.045) when recorded on microelectrodes compared with clinical macroelectrodes. Although gamma-IEDs comprised only a subset of IEDs, they were strongly associated with electrodes in the seizure onset zone (SOZ) compared with the surrounding brain regions (p = 0.004), in sharp contrast to IEDs without preceding gamma oscillations that were often also detected outside of the SOZ. Similar to prior studies, isolated pathologic high-frequency oscillations in the gamma (30-100 Hz) and higher (100-600 Hz) frequency range, not associated with an IED, were also found to be associated with SOZ. CONCLUSIONS: The occurrence of locally generated gamma oscillations preceding IEDs suggests a mechanistic role for gamma in pathologic network activity generating IEDs. The results show a strong association between SOZ and gamma-IEDs. The potential clinical application of gamma-IEDs for mapping pathologic brain regions is intriguing, but will require future prospective studies.

DPPX potassium channel antibody: frequency, clinical accompaniments, and outcomes in 20 patients.

OBJECTIVE: To describe the detection frequency and clinical associations of immunoglobulin G (IgG) targeting dipeptidyl-peptidase-like protein-6 (DPPX), a regulatory subunit of neuronal Kv4.2 potassium channels. METHODS: Specimens from 20 patients evaluated on a service basis by tissue-based immunofluorescence yielded a synaptic immunostaining pattern consistent with DPPX-IgG (serum, 20; CSF, all 7 available). Transfected HEK293 cell-based assay confirmed DPPX specificity in all specimens. Sixty-nine patients with stiff-person syndrome and related disorders were also evaluated by DPPX-IgG cell-based assay. RESULTS: Of 20 seropositive patients, 12 were men; median symptom onset age was 53 years (range, 13-75). Symptom onset was insidious in 15 and subacute in 5. Twelve patients reported prodromal weight loss. Neurologic disorders were multifocal. All had one or more brain or brainstem manifestations: amnesia (16), delirium (8), psychosis (4), depression (4), seizures (2), and brainstem disorders (15; eye movement disturbances [8], ataxia [7], dysphagia [6], dysarthria [4], respiratory failure [3]). Nine patients reported sleep disturbance. Manifestations of central hyperexcitability included myoclonus (8), exaggerated startle (6), diffuse rigidity (6), and hyperreflexia (6). Dysautonomia involved the gastrointestinal tract (9; diarrhea [6], gastroparesis, and constipation [3]), bladder (7), cardiac conduction system (3), and thermoregulation (1). Two patients had B-cell neoplasms: gastrointestinal lymphoma (1), and chronic lymphocytic leukemia (1). Substantial neurologic improvements followed immunotherapy in 7 of 11 patients with available treatment data. DPPX-IgG was not detected in any of the stiff-person syndrome patients. CONCLUSIONS: DPPX-IgG is a biomarker for an immunotherapy-responsive multifocal neurologic disorder of the central and autonomic nervous systems.

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.

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.

Childhood onset of stiff-man syndrome.

IMPORTANCE: Reports of pediatric-onset stiff-man syndrome (SMS) are rare. This may be an underrecognized disorder in child neurology practice. OBJECTIVE: To describe patients with disorders in the SMS spectrum beginning in childhood. DESIGN, SETTING, AND PARTICIPANTS: This study was a medical record review and serological evaluation conducted at child and adult neurology clinics at the Mayo Clinic, Rochester, Minnesota. Systematic review of the literature was conducted of patients who presented from 1984-2012 with onset of symptomatic SMS occurring at age 18 years or younger. MAIN OUTCOMES AND MEASURES: Response to symptomatic and immunotherapies, patient and physician reported, including modified Rankin scale. RESULTS: We identified 8 patients with childhood-onset SMS, representing 5% of patients with SMS evaluated at Mayo Clinic during a period of 29 years (4 were girls). The median age at symptom onset was 11 years (range, 1-14 years). The diagnosis in 3 patients was not established until adulthood (median symptom duration at diagnosis, 14 years; range, 0-46 years). The phenotypes encountered were: classic SMS (n = 5, involving the low back and lower extremities), variant SMS (n = 2, limited to 1 limb [with dystonic posture] or back), and progressive encephalomyelitis with rigidity and myoclonus (n = 1). Initial misdiagnoses included functional movement disorder (n = 2), generalized dystonia and parkinsonism (n = 1), and hereditary spastic paraparesis (n = 1). Six patients had 1 or more coexisting autoimmune disorders: type 1 diabetes mellitus (n = 4), thyroid disease (n = 2), and vitiligo (n = 2). Serologic study results revealed glutamic acid decarboxylase 65-IgG in all cases (median value, 754 nmol/L; range, 0.06-3847 nmol/L; normal value, ≤ 0.02 nmol/L) and glycine receptor antibody in 3 cases. Improvements were noted with symptomatic therapy (diazepam, 6 of 6 patients treated, and oral baclofen, 3 of 3 treated) and immunotherapy (intravenous immune globulin, 3 of 4 treated and plasmapheresis, 3 of 4 treated). The 3 patients with glycine receptor antibody all improved with immunotherapy. At last follow-up, 4 patients had mild or no symptoms, but 4 had moderate or severe residual symptoms and required maintenance symptomatic therapy (n = 5) and immunotherapy (n = 4). Ten of 12 pediatric SMS cases identified by literature review had a severe whole-body phenotype resembling progressive encephalomyelitis with rigidity and myoclonus. CONCLUSIONS AND RELEVANCE: Childhood-onset SMS is a rare but underrecognized and treatable disorder. Serological and electrophysiological testing aid diagnosis.