Clinical Spectrum of Stiff Person Syndrome: A Review of Recent Reports

Background: “Classic” stiff person syndrome (SPS) features stiffness, anti-glutamic acid decarboxylase (anti-GAD) antibodies, and other findings. Anti-GAD antibodies are also detected in some neurological syndromes (such as ataxia) in which stiffness is inconsistently present. Patients with otherwise “classic” SPS may either lack anti-GAD antibodies or be seropositive for others. Hence, SPS cases appear to fall within a clinical spectrum that includes conditions such as progressive encephalomyelitis with rigidity and myoclonus (PERM), which exhibits brainstem and autonomic features. We have compiled herein SPS-spectrum cases reported since 2010, and have segregated them on the basis of likely disease mechanism (autoimmune, paraneoplastic, or cryptogenic) for analysis. Methods: The phrases “stiff person syndrome”, “PERM”, “anti-GAD antibody syndrome”, and “glycine receptor antibody neurological disorders” were searched for in PubMed in January 2015. The results were narrowed to 72 citations after excluding non-English and duplicate reports. Clinical descriptions, laboratory data, management, and outcomes were categorized, tabulated, and analyzed. Results: Sixty-nine autoimmune, 19 paraneoplastic, and 13 cryptogenic SPS-spectrum cases were identified. SPS was the predominant diagnosis among the groups. Roughly two-thirds of autoimmune and paraneoplastic cases were female. Anti-GAD antibodies were most frequently identified, followed by anti-amphiphysin among paraneoplastic cases and by anti-glycine receptor antibodies among autoimmune cases. Benzodiazepines were the most commonly used medications. Prognosis seemed best for cryptogenic cases; malignancy worsened that of paraneoplastic cases. Discussion: Grouping SPS-spectrum cases by pathophysiology provided insights into work-up, treatment, and prognosis. Ample phenotypic and serologic variations are present within the categories. Ruling out malignancy and autoimmunity is appropriate for suspected SPS-spectrum cases

Study protocol: A cross-sectional survey of clinicians to identify barriers to clinical practice guideline implementation in the assessment and treatment of persistent tic disorders

INTRODUCTION: Eight members of the International Parkinson\u27s Disease and Movement Disorders Society Tic and Tourette Syndrome Study Group formed a subcommittee to discuss further barriers to practice guideline implementation. Based on expert opinion and literature review, the consensus was that practice variations continue to be quite broad and that many barriers in different clinical settings might negatively influence the adoption of the American Academy of Neurology and the European Society for the Study of Tourette Syndrome published guidelines. OBJECTIVES: 1) To identify how clinical practices diverge from the existing American Academy of Neurology and European Society for the Study of Tourette Syndrome guidelines, and 2) to identify categories of barriers leading to these clinical care gaps. METHODS AND ANALYSIS: This article presents the methodology of a planned cross-sectional survey amongst healthcare professionals routinely involved in the clinical care of patients with persistent tic disorders, aimed at 1) identifying how practices diverge from the published guidelines; and 2) identifying categories of barriers leading to these clinical care gaps. Purposeful sampling methods are used to identify and recruit critical persistent tic disorders stakeholders. The analysis will use descriptive statistics

A Case of Myoclonus–Dystonia Responding to Low-frequency Pallidal Stimulation

Background: High frequency pallidal stimulation has been shown to improve various types of dystonia, including myoclonus-dystonia. Case Report: We report a case of epsilon sarcoglycan mutation-negative myoclonus-dystonia (MD) with response to low frequency bilateral pallidal stimulation. Discussion: Low frequency pallidal stimulation provides an effective means of treating various dystonias, regardless of genetic status, as in our case, as it provides increased programming options with less adverse effects

Clinical Practice Patterns in Tic Disorders Among Movement Disorder Society Members

[Background] Tic disorders belong to the broad spectrum of pediatric and adult movement disorders. The wide variability in clinical presentations, applied assessment tools, and treatments are poorly understood.[Objectives] To map practices and knowledge base of movement disorder clinicians concerning clinical features, pathophysiology, and treatment approaches in tic disorders. [Methods] A 33-item survey was developed by the Tic Disorders and Tourette syndrome Study Group members of the Movement Disorder Society. The survey was distributed to the complete society membership and included responses from 346 members, 314 of whom reported treating tic disorders. [Results] Approximately one third of survey respondents (35%) frequently evaluated patients with tics. The data revealed widespread use of existing guidelines (about 70%) and screening for comorbid disorders (>90%). The most common investigations used to rule out secondary causes of tics were imaging (92%), laboratory tests (66%) and neurophysiology (38%). Functional tics were the second most common tic etiology following primary tics. Only 27% of respondents reported confidence in knowledge about tic pathogenesis. Top rated interventions to treat tics were psychoeducation, cognitive behavioral intervention for tics (CBIT) and treatment for neuropsychiatric comorbidities. Antipsychotics were ranked as the most effective pharmacologic tic intervention. Conclusions: The majority of movement disorders specialists do not frequently encounter tics. There was sparse knowledge about tic pathophysiology. Psychoeducation, CBIT, the treatment of neuropsychiatric comorbidities and use of antipsychotics emerged as the most common interventions to treat tics. These results provide insight into what will be needed to improve the diagnosis and treatment of tic disorders.CG is supported by the Freigeist Fellowship of the VolkswagenStiftung. He has served as ad hoc advisory board to Biomarin and received honoraria from the International Parkinsons Disease and Movement Disorders Society for educational activities

Evidence for the use of pimavanserin in the treatment of Parkinson’s disease psychosis

Parkinson’s disease (PD) is a progressive neurodegenerative disorder with both motor and nonmotor symptoms (NMS), leading to significant morbidity and caregiver burden. Psychosis is common but is under recognized by physicians. When present, it increases the patient’s risk of hospitalization and nursing home placement and caregiver burden. Although the atypical antipsychotic agent, clozapine, has been considered the gold standard treatment, severe agranulocytosis in 0.38% of patients and more commonly milder leukopenia, resulting in frequent blood testing, limit its use. Pimavanserin, a 5HT2A receptor inverse agonist, has been shown to reduce psychosis in PD without worsening motor symptoms. It is therefore a welcome therapeutic option for this devastating NMS

Isolated Hyperreligiosity in a Patient with Temporal Lobe Epilepsy

A 40-year-old man with history of temporal lobe epilepsy presented to the emergency department with hyperreligiosity after medication noncompliance. After medications were resumed, he returned to baseline. Many famous prophets are believed to have suffered epilepsy. Waxman and Geschwind described a group of traits in patients with temporal lobe epilepsy consisting of hyperreligiosity, hypergraphia, altered sexual behavior, aggressiveness, preoccupation with details, and circumstantiality. The incidence of religious experiences ranges from 0.3 to 3.1 percent in patients with epilepsy. Religious experiences can be ictal, interictal, or postictal. Treatment is aimed at the underlying seizure etiology

Pathophysiology and Treatment of Alien Hand Syndrome

Background: Alien hand syndrome (AHS) is a disorder of involuntary, yet purposeful, hand movements that may be accompanied by agnosia, aphasia, weakness, or sensory loss. We herein review the most reported cases, current understanding of the pathophysiology, and treatments.Methods: We performed a PubMed search in July of 2014 using the phrases &ldquo;alien hand syndrome,&rdquo; &ldquo;alien hand syndrome pathophysiology,&rdquo; &ldquo;alien hand syndrome treatment,&rdquo; and &ldquo;anarchic hand syndrome.&rdquo; The search yielded 141 papers (reviews, case reports, case series, and clinical studies), of which we reviewed 109. Non‐English reports without English abstracts were excluded.Results: Accumulating evidence indicates that there are three AHS variants: frontal, callosal, and posterior. Patients may demonstrate symptoms of multiple types; there is a lack of correlation between phenomenology and neuroimaging findings. Most pathologic and functional imaging studies suggest network disruption causing loss of inhibition as the likely cause. Successful interventions include botulinum toxin injections, clonazepam, visuospatial coaching techniques, distracting the affected hand, and cognitive behavioral therapy.Discussion: The available literature suggests that overlap between AHS subtypes is common. The evidence for effective treatments remains anecdotal, and, given the rarity of AHS, the possibility of performing randomized, placebo‐controlled trials seems unlikely. As with many other interventions for movement disorders, identifying the specific functional impairments caused by AHS may provide the best guidance towards individualized supportive care.</p

Neurosurgeons perspective on the shift towards earlier use of deep brain stimulation for Parkinson disease

Background: The US Food and Drug Administration approved in 2015 the use of deep brain stimulation for Parkinson disease after “four years duration and with recent onset of motor complications”. The aim of this study was to identify neurosurgeons’ attitudes and perspectives around the use of deep brain stimulation for Parkinson disease earlier in the disease course. Methods: An anonymous survey examining attitudes and perceptions towards deep brain stimulation practice and timing in Parkinson disease was developed by the study team and distributed by the American Society for Stereotactic and Functional Neurosurgeons to its members. Results from 32 subjects with answers to at least 50% of the survey were included. Data were analyzed with descriptive statistics and chi-square test. Results: Motor fluctuations, dyskinesia, quality of life impairment, and medically refractory tremor were the most important reasons to proceed with deep brain stimulation, which was overall considered more useful after the onset of motor symptoms. Unresponsiveness to levodopa, cognitive impairment, and unclear diagnosis were important reasons not to consider deep brain stimulation. Earlier surgery was considered to be less risky compared to later in the disease progression. Ten out of 25 neurosurgeons reported considering deep brain stimulation as a therapeutic option after a minimum disease duration of three to four years. Conclusions: We conclude that neurosurgeons support the use of earlier deep brain stimulation, but not preceding motor complications. Further research surrounding the benefits and adverse effects of earlier deep brain stimulation is needed to guide practice and better inform potential candidates