Anna Hohler

Impaired olfaction and other prodromal features in the Parkinson At-Risk Syndrome Study.

To test the association between impaired olfaction and other prodromal features of PD in the Parkinson At‐Risk Syndrome Study. The onset of olfactory dysfunction in PD typically precedes motor features, suggesting that olfactory testing could be used as a screening test. A combined strategy that uses other prodromal nonmotor features, along with olfactory testing, may be more efficient than hyposmia alone for detecting the risk of PD. Individuals with no neurological diagnosis completed a mail survey, including the 40‐item University of Pennsylvania Smell Identification Test, and questions on prodromal features of PD. The frequency of reported nonmotor features was compared across individuals with and without hyposmia. A total of 4,999 subjects completed and returned the survey and smell test. Of these, 669 were at or below the 15th percentile based on age and gender, indicating hyposmia. Hyposmics were significantly more likely to endorse nonmotor features, including anxiety and depression, constipation, and rapid eye movement sleep behavior disorder symptoms, and to report changes in motor function. Twenty‐six percent of subjects with combinations of four or more nonmotor features were hyposmic, compared to 12% for those reporting three or fewer nonmotor features (P < 0.0001). Hyposmia is associated with other nonmotor features of PD in undiagnosed individuals. Further assessment of hyposmic subjects using more specific markers for degeneration, such as dopamine transporter imaging, will evaluate whether combining hyposmia and other nonmotor features is useful in assessing the risk of future neurodegeneration.

Effect of Deutetrabenazine on Chorea Among Patients With Huntington Disease: A Randomized Clinical Trial

IMPORTANCE Deutetrabenazine is a novel molecule containing deuterium, which attenuates CYP2D6 metabolism and increases active metabolite half-lives and may therefore lead to stable systemic exposure while preserving key pharmacological activity. OBJECTIVE To evaluate efficacy and safety of deutetrabenazine treatment to control chorea associated with Huntington disease. DESIGN, SETTING, AND PARTICIPANTS Ninety ambulatory adults diagnosed with manifest Huntington disease and a baseline total maximal chorea score of 8 or higher (range, 0-28; lower score indicates less chorea) were enrolled from August 2013 to August 2014 and randomized to receive deutetrabenazine (n = 45) or placebo (n = 45) in a double-blind fashion at 34 Huntington Study Group sites. INTERVENTIONS Deutetrabenazine or placebo was titrated to optimal dose level over 8 weeks and maintained for 4 weeks, followed by a 1-week washout. MAIN OUTCOMES AND MEASURES Primary end point was the total maximal chorea score change from baseline (the average of values from the screening and day-0 visits) to maintenance therapy (the average of values from the week 9 and 12 visits) obtained by in-person visits. This study was designed to detect a 2.7-unit treatment difference in scores. The secondary end points, assessed hierarchically, were the proportion of patients who achieved treatment success on the Patient Global Impression of Change (PGIC) and on the Clinical Global Impression of Change (CGIC), the change in 36-Item Short Form- physical functioning subscale score (SF-36), and the change in the Berg Balance Test. RESULTS Ninety patients with Huntington disease (mean age, 53.7 years; 40 women [44.4%]) were enrolled. In the deutetrabenazine group, the mean total maximal chorea scores improved from 12.1 (95% CI, 11.2-12.9) to 7.7 (95% CI, 6.5-8.9), whereas in the placebo group, scores improved from 13.2 (95% CI, 12.2-14.3) to 11.3 (95% CI, 10.0-12.5); the mean between-group difference was -2.5 units (95% CI, -3.7 to -1.3) (P < .001). Treatment success, as measured by the PGIC, occurred in 23 patients (51%) in the deutetrabenazine group vs 9 (20%) in the placebo group (P = .002). As measured by the CGIC, treatment success occurred in 19 patients (42%) in the deutetrabenazine group vs 6 (13%) in the placebo group (P = .002). In the deutetrabenazine group, the mean SF-36 physical functioning subscale scores decreased from 47.5 (95% CI, 44.3-50.8) to 47.4 (44.3-50.5), whereas in the placebo group, scores decreased from 43.2 (95% CI, 40.2-46.3) to 39.9 (95% CI, 36.2-43.6), for a treatment benefit of 4.3 (95% CI, 0.4 to 8.3) (P = .03). There was no difference between groups (mean difference of 1.0 unit; 95% CI, -0.3 to 2.3; P = .14), for improvement in the Berg Balance Test, which improved by 2.2 units (95% CI, 1.3-3.1) in the deutetrabenazine group and by 1.3 units (95% CI, 0.4-2.2) in the placebo group. Adverse event rates were similar for deutetrabenazine and placebo, including depression, anxiety, and akathisia. CONCLUSIONS AND RELEVANCE Among patients with chorea associated with Huntington disease, the use of deutetrabenazine compared with placebo resulted in improved motor signs at 12 weeks. Further research is needed to assess the clinical importance of the effect size and to determine longer-term efficacy and safety. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01795859.

Effectiveness of an Inpatient Multidisciplinary Rehabilitation Program for People With Parkinson Disease

Background and Purpose: In the outpatient setting, it can be difficult to effectively manage the complex medical and rehabilitation needs of people with Parkinson disease (PD). A multidisciplinary approach in the inpatient rehabilitation environment may be a viable alternative. The purposes of this study were: (1) to investigate the effectiveness of an inpatient rehabilitation program for people with a primary diagnosis of PD, (2) to determine whether gains made were clinically meaningful, and (3) to identify predictors of rehabilitation outcome. Subjects: Sixty-eight subjects with a diagnosis of PD were admitted to an inpatient rehabilitation hospital with a multidisciplinary movement disorders program. Methods: Subjects participated in a rehabilitation program consisting of a combination of physical therapy, occupational therapy, and speech therapy for a total of 3 hours per day, 5 to 7 days per week, in addition to pharmacological adjustments based on data collected daily. A pretest-posttest design was implemented. The differences between admission and discharge scores on the Functional Independence Measure (FIM) (total, motor, and cognitive scores), Timed “Up & Go” Test, 2-Minute Walk Test, and Finger Tapping Test were analyzed. Results: An analysis of data obtained for the 68 subjects admitted with a diagnosis of PD revealed significant improvements across all outcome measures from admission to discharge. Subjects with PD whose medications were not adjusted during their admission (rehabilitation only) (n=10) showed significant improvements in FIM total, motor, and cognitive scores. Improvements exceeded the minimal clinically important difference in 71% of the subjects. Prior level of function at admission accounted for 20% of the variance in the FIM total change score. Discussion and Conclusion: The results suggest that subjects with a diagnosis of PD as a primary condition benefited from an inpatient rehabilitation program designed to improve functional status.

Ehlers–Danlos Syndrome and Postural Tachycardia Syndrome: A relationship study

OBJECTIVE This study examines a possible relationship between Ehlers-Danlos Syndrome (EDS) and Postural Tachycardia Syndrome (POTS). DESIGN/METHODS We retrospectively reviewed 109 medical records of patients suffering from autonomic dysfunction exhibiting at least one POTS symptom from one urban clinic for EDS and POTS diagnoses between 2006 and 2013. The presence of EDS within the POTS and non-POTS populations was calculated and compared to that of the general population. RESULTS The review revealed 39 (36F:3M) patients with POTS (mean ± SD age, 32.5 ± 11.8 years) with 7 cases of EDS yielding a prevalence of 18% (95% exact CI: 8%, 34%), a statistically significant difference from the suggested prevalence of EDS in the general population of 0.02% (p<0.0001). 70 patients (53F:17M) without POTS (mean ± SD age, 51.1 ± 14.7 years) contained 3 cases of EDS, yielding a prevalence of 4% (95% exact CI: 1%, 12%), a statistically significant difference from the general population (p<0.0001). The prevalence of EDS was significantly higher in the POTS group compared to the non-POTS group (p=0.0329). The odds ratio comparing the odds of EDS for POTS versus non-POTS patients is 4.9 (95% CI: 1.2, 20.1). CONCLUSION The presence of EDS may be significantly higher in patients with POTS than that of the general population and in autonomic patients without POTS. We suspect an additional underlying mechanism of POTS caused by EDS.

Differences in motor and cognitive function in patients with Parkinson's disease with and without orthostatic hypotension.

ABSTRACT Patients with Parkinsons disease (PD) often present with orthostatic hypotension (OH) as a result of the dysautonomia associated with the disease or as a side effect of the dopaminergic medications used to treat the disease. The purpose of this study was to investigate differences in motor and cognitive function in patients with PD with and without OH. Forty-four patients with a diagnosis of PD were evaluated and stratified by the presence of OH based on orthostatic blood pressure recordings. Both groups underwent assessments of motor and cognitive function. OH was present in 17 of 44 patients (39%) with PD. These patients with OH had significantly lower scores in gross motor, balance, and cognitive function (p < .05). No significant difference between groups was found in the finger tapping scores. These results suggest that patients with PD should be routinely screened for OH as it commonly occurs and may negatively impact gross motor, balance, and cognitive function.

The American Academy of Neurology position statement on abuse and violence

Neurologists see patients with neurologic disabilities that render them susceptible to abuse or neglect. They also encounter patients with neurologic dysfunction that may be either directly or indirectly related to maltreatment. In 2008, the American Medical Association (AMA) encouraged physicians to “routinely inquire about the family violence histories of their patients, as this knowledge is essential for effective diagnosis and care.”1 Consensus-based guidelines for identification of intimate partner violence (IPV) have been adopted by numerous medical specialty organizations.2,–,11 The US Department of Health and Human Services has recommended that women be screened and counseled for domestic abuse.12 The consequences of not asking about IPV might include further physical and emotional harm, treatment failure, and when children are exposed, perpetuation of the intergenerational cycle of abuse.13,–,15 Providing resources to those being abused can result in improved outcomes.16 Further, identification of an abuse history may influence the assessment and treatment of presenting health concerns.17,18 By identifying this issue, and providing an appropriate referral, neurologists may improve quality of life and potentially ameliorate neurologic disability. The AAN is endorsing the assessment of abuse and neglect in our patients and supports the education of the neurologic community to achieve this end. Additional research on the physiologic and psychological consequences of abuse may lead to better treatment strategies to prevent related adverse health outcomes. Abuse may be defined in a variety of ways. The …

Treatment of idiopathic intracranial hypertension with gastric bypass surgery

Idiopathic intracranial hypertension (IIH) is defined by elevated intracranial pressure and associated headaches, changes in vision and pulsatile tinnitus, among other symptoms. It occurs most frequently in young, obese women. Gastric bypass surgery has been used to treat morbid obesity and its comorbidities, and IIH has recently been considered among these indications. We present a case report of a 29-year-old female with a maximum BMI of 50.3 and a 5-year history of severe headaches and moderate papilledema due to IIH. She also developed migraine headaches. After a waxing and waning course and various medical treatments, the patient underwent laparoscopic Roux-en-Y gastric bypass surgery with anterior repair of hiatal hernia. Dramatic improvement in IIH headaches occurred by 4 months postprocedure and was maintained at 1 year, when she reached her weight plateau with a BMI of 35. Presurgery migraines persisted. This adds to the small number of case reports and retrospective analyses of the successful treatment of IIH with gastric bypass surgery, and brings this data from the surgical literature into the neurological domain. It offers insight into an early time course for symptom resolution, and explores the impact of weight-loss surgery on migraine headaches. This treatment modality should be further investigated prospectively to analyze the rate of headache improvement with weight loss, the amount of weight loss needed for clinical improvement, and the possible correlation with improvement in papilledema.

Onset of Creutzfeldt-Jakob disease mimicking an acute cerebrovascular event.

Creutzfeldt–Jakob disease (CJD) usually presents as a rapidly progressive dementia, and is associated with motor abnormalities. EEG findings may include generalized periodic discharges, slowing, or may be normal. CJD may present with various neurobehavioral abnormalities. Symptoms are classically subacute. Here we describe an autopsy-proven case of CJD in a patient who presented with an acute onset focal neurobehavioral syndrome suggestive of a cerebrovascular event. Acute stroke-like onset is an uncommon clinical presentation.1–3 A 62-year-old right-handed man presented with memory and naming deficits that began immediately after a Dupetryns contracture release. He was evaluated in the neurology clinic 4 months later. His wife reported acute onset of symptoms that were noted immediately after he awoke from general anesthesia. He had previously been highly functioning (IQ = 148). On neurobehavioral testing, he was alert and attentive but had no spontaneous speech output. His general …

Quality improvement in neurology: Parkinson disease update quality measurement set: Executive summary

Approximately 630,000 people in the United States carried a diagnosis of Parkinson disease (PD) in 2010, and worldwide estimates indicate that up to 10 million individuals may be diagnosed currently.1,2 The national economic burden of PD was estimated to exceed

A survey-based analysis of symptoms in patients with postural orthostatic tachycardia syndrome

14.4 billion in 2010.1 PD is a heterogeneous disorder with motor and nonmotor features that are often underdiagnosed and, in turn, provided limited treatment options. The American Academy of Neurology (AAN) created a quality measurement set in 2010 to provide a framework for measuring progress on addressing these treatment gaps in care.3