Neuroimaging Pearls from the MDS Congress Video Challenge. Part 2: Acquired Disorders.

The MDS Video Challenge continues to be the one of most widely attended sessions at the International Congress. Although the primary focus of this event is the presentation of complex and challenging cases through videos, a number of cases over the years have also presented an unusual or important neuroimaging finding related to the case. We reviewed the previous Video Challenge cases and present here a selection of those cases which incorporated such imaging findings. We have compiled these "imaging pearls" into two anthologies. The first focuses on pearls where the underlying diagnosis was a genetic condition. This second anthology focuses on imaging pearls in cases where the underlying condition was acquired. For each case we present brief clinical details along with neuroimaging findings, the characteristic imaging findings of that disorder and, finally, the differential diagnosis for the imaging findings seen.

Parkinsonism and cerebrovascular disease.

The relationship between cerebrovascular disease and parkinsonism is commonly seen in everyday clinical practice but remains ill-defined and under-recognised with little guidance for the practising neurologist. We attempt to define this association and to illustrate key clinical, radiological and pathological features of the syndrome of Vascular Parkinsonism (VaP). VaP is a major cause of morbidity in the elderly associated with falls, hip fractures and cognitive impairment. Although acute parkinsonism is reported in the context of an acute cerebrovascular event, the vast majority of VaP presents as an insidious syndrome usually in the context of vascular risk factors and radiological evidence of small vessel disease. There may be an anatomic impact on basal ganglia neuronal networks, however the effect of small vessel disease (SVD) on these pathways is not clear. There are now established reporting standards for radiological features of SVD on MRI. White matter hyperintensities and lacunes have been thought to be the representative radiological features of SVD but other features such as the perivascular space are gaining more importance, especially in context of the glymphatic system. It is important to consider VaP in the differential diagnosis of Parkinson disease (PD) and in these situations, neuroimaging may offer diagnostic benefit especially in those patients with atypical presentations or refractoriness to levodopa. Proactive management of vascular risk factors, monitoring of bone density and an exercise program may offer easily attainable therapeutic targets in PD and VaP. Levodopa therapy should be considered in patients with VaP, however the dose and effect may be different from use in PD. This article is part of the Special Issue "Parkinsonism across the spectrum of movement disorders and beyond" edited by Joseph Jankovic, Daniel D. Truong and Matteo Bologna.

Epidural Blood Patch as a Diagnostic and Therapeutic Intervention in Spontaneous Intracranial Hypotension: A Novel Approach to Management.

OBJECTIVE: Spontaneous intracranial hypotension (SIH) remains a diagnostic and therapeutic challenge. Nonspecific clinical features and a reluctance to treat without confirmatory imaging evidence undermine management. Investigations are often insensitive and expensive, with many patients continuing to an epidural blood patch (EBP) despite negative results. Current diagnostic standards are based on a literature base skewed toward difficult-to-treat cases at specialty centers. This study aims to develop a robust diagnostic and treatment algorithm in real-life clinical practice by 1) investigating the prognostic utility of symptoms of SIH and results of associated investigation from which a scoring system is derived and 2) analyzing the role of EBP as a diagnostic and treatment tool. METHODS: This is a retrospective study of 86 patients fulfilling clinical criteria for SIH and undergoing EBP, with follow-up ranging from 1 month to 15 years, using patient medical records and an online questionnaire. RESULTS: Although specific and prognostically significant, magnetic resonance imaging of the brain, magnetic resonance imaging of the spine, and symptom-based scoring systems were too insensitive to be of practical use. Most patients with positive and sustained responses to EBP did not meet current criteria for diagnosis. The 72-hour response to the first EBP was found to be highly specific and sensitive in the diagnosis of SIH in our cohort. CONCLUSIONS: This study supports the utility of EBP as a safe, accessible, and accurate diagnostic and therapeutic tool. We propose a simple treatment algorithm that facilitates diagnosis, treatment, and prediction of long-term outcomes in this challenging condition.

Functional outcomes of an integrated Parkinson's Disease Wellbeing Program.

INTRODUCTION: There is growing evidence that exercise provides benefit in treating motor and non-motor symptoms in Parkinson's disease (PD). OBJECTIVES: The aims of this study were to determine (a) whether a 5-week PD-specific program resulted in sustained physical and psychosocial benefits, and (b) the relationship between patient characteristics, exercise, falls and physical and psychosocial parameters. DESIGN: Single-centre prospective observational study. METHODS: A total of 135 consecutive patients with mild-to-moderate PD underwent a 5-week PD-specific education and exercise program from August 2013 to March 2015. Gait, mobility and psychosocial measures were compared at baseline, 6 weeks and 12 months. RESULTS: Significant improvements in physical (walking distance in 2 minutes, number of "Sit To Stands" in 30 seconds, time in seconds taken to "Timed Up and Go," fast gait velocity over 10 m, Berg Balance Scale [BBS]) and psychosocial (quality of life (QoL) [PDQ-39], depression and anxiety [DASS-21], and fatigue [PSF-16]) measures were seen at 6 weeks (all P < .01) with physical improvements sustained at 12 months (all P < .001). The number of patients at 12 months with ≥1 fall reduced from 66% to 33%, and the number not exercising reduced from 42% to 21%. A lack of exercise correlated with ≥1 fall at 12 months (OR 3.39, 95% CI 1.36-8.39, P = .009). It was also associated with poorer balance and psychosocial parameters at 12 months (all P < .05). CONCLUSIONS: Patients recruited into a 5-week Parkinson's disease education and exercise program achieved significant 12-month benefits in physical but not psychosocial measures. Patients with ≥1 fall post-treatment were less likely to have been exercising at 12-month follow-up.

Real-world effectiveness of onabotulinumtoxinA treatment for the prevention of headaches in adults with chronic migraine in Australia: a retrospective study.

BACKGROUND: OnabotulinumtoxinA (BOTOX®, Allergan plc, Dublin, Ireland) is approved for the preventive treatment of headaches in adult patients with chronic migraine (CM) in Australia by the country's reimbursement mechanism for medicines, the Pharmaceutical Benefits Scheme (PBS). To our knowledge, this study represents the first focused report evaluating real-world evidence of onabotulinumtoxinA treatment via the PBS in Australian clinics. METHODS: This study reviewed the medical records of adults with inadequately controlled CM from 7 private neurology practices in Australia who, beginning in March 2014, received PBS-subsidized onabotulinumtoxinA per product labelling for the first time. The primary effectiveness measure was the percentage of patients achieving a response defined by 50% or greater reduction in headache days from baseline after 2 treatment cycles. Additional data were recorded in the case report form when available and included demographics, clinical characteristics, headache severity and frequency, Headache Impact Test (HIT-6) score, medication use, and days missed of work or study at baseline, after 2 treatment cycles, and at last follow-up. Differences in mean changes from baseline were evaluated with a 1-tailed t-test or Pearson's chi-squared test (p < 0.05). RESULTS: The study population included 211 patients with a mean (SD) of 25.2 (5.3) monthly headache days at baseline. In the primary outcome analysis, 74% of patients achieved a response, with a mean (SD) of 10.6 (7.9) headache days after 2 treatment cycles (p < 0.001). Secondary effectiveness outcomes included mean (SD) reductions in HIT-6 score of - 11.7 (9.8) and - 11.8 (12.2) after 2 treatment cycles (p < 0.001) and final follow-up (p < 0.001), respectively, and mean (SD) decreases in days per month of acute pain medication use of - 11.5 (7.6) after 2 treatment cycles (p < 0.001) and - 12.7 (8.1) at final follow-up (p < 0.001). CONCLUSION: This study provides additional clinical evidence for the consistent effectiveness of onabotulinumtoxinA for the treatment of CM in Australia. This effectiveness was made evident by reductions in migraine days, severe headache days, and HIT-6 scores from baseline.

Impact of small vessel disease on severity of motor and cognitive impairment in Parkinson's disease.

BACKGROUND: Subcortical small vessel disease and vascular risk factors are associated with motor and cognitive impairment. In this study we examined the relationship between these factors and the severity of motor impairment and dementia in pathologically-confirmed Parkinson's disease (PD). METHODS: The extent and severity of small vessel disease (SVD) was assessed pathologically in 77 patients with PD. The severity of motor impairment was determined using a cumulative index derived from longitudinal measures of Hoehn and Yahr score. The presence of dementia was scored using the Clinical Dementia Rating. The presence or absence of vascular risk factors and stroke were also recorded. Interactions were assessed using stepwise multiple regression analyses. RESULTS: Significant correlations were demonstrated between perivascular pallor in the globus pallidus interna and the Hoehn and Yahr stage and between increasing Braak PD stage, the number of vascular risk factors and dementia. Among the vascular risk factors, hypertension was the only variable to independently correlate with dementia. SVD pathology did not correlate with dementia in our cohort. CONCLUSIONS: This study demonstrates an association between SVD and motor impairment, and between vascular risk factors, particularly hypertension, and dementia in PD and highlights the need to manage vascular co-morbidities in PD patients.

The Effect of Biofeedback as a Psychological Intervention in Multiple Sclerosis: A Randomized Controlled Study.

BACKGROUND: Relaxation, mindfulness, social support, and education (RMSSE) have been shown to improve emotional symptoms, coping, and fatigue in multiple sclerosis (MS). Biofeedback was trialed as a psychological intervention, designed to improve self-control, in two groups of patients with MS. Both groups received RMSSE, and one group additionally received biofeedback. METHODS: Forty people with relapsing-remitting MS were recruited from three sites in Sydney, Australia. The mean disability score (Expanded Disability Status Scale; EDSS) was 2.41 ± 1.46 (95% confidence interval [CI], 1.46-3.36); the mean age in years was 45.9 ± 12.42 (95% CI, 41.92-49.87). Participants were randomly assigned to two active treatment groups (n = 20 per group). All participants received one 1-hour session per week for 3 weeks of RMSSE, while biofeedback equipment measured breathing rate and muscle tension. Members of one group used biofeedback screens to regulate physiological response. RESULTS: Whole-group pre- and post-treatment scores demonstrated a reduction of 38% for anxiety and 39% for depression scores (P = .007 and P = .009, respectively). A post-treatment comparison failed to demonstrate any significant difference between the two active treatment groups in anxiety and depression scores. The biofeedback group showed significant pre- to post-treatment improvement or trends toward improvement in anxiety, fatigue, and stress (P = .05, .02, and .03, respectively). Comparison of pre-post treatment results between groups showed improvements for the biofeedback group in breathing rate and muscle tension (P = .06 and .09). CONCLUSIONS: For relapsing-remitting MS patients receiving biofeedback in addition to RMSSE, there was a demonstrable reduction in anxiety, fatigue, and stress. There was also a trend toward significant reduction of breathing rate and muscle tension in favor of biofeedback.

Rebound exacerbation multiple sclerosis following cessation of oral treatment.

BACKGROUND: Multiple sclerosis (MS) management is changing, revolutionized by oral agents. Immune Reconstitution Inflammatory Syndrome (IRIS) describes exaggerated response to both exogenous (infective) and endogenous (non-infective) antigens. METHODS: This paper reports two cases of MS "rebound" following withdrawal of oral treatments. RESULTS: Two patients, with suboptimal response to interferons, trialled oral MS treatment (fingolimod and BG12) with excellent response. Upon cessation both experienced MS "rebound" which responded to steroids. CONCLUSIONS: "Rebound" may occur following withdrawal of oral MS therapies. Patients should be advised accordingly and possibly started on alternative treatment before the immunomodulating effect of therapy has subsided.

Small-vessel disease in patients with Parkinson's disease: a clinicopathological study.

Few studies have examined the relationship between cerebrovascular disease, vascular risk factors, and Parkinson's disease (PD), although 1 study found small-vessel disease (SVD) to be the main subtype of cerebrovascular disease. In this study we compared the extent and topography of SVD and assessed associated vascular risk factors in autopsy-proven PD cases and community-dwelling controls. Seventy-seven PD and 32 control brains from the Sydney Brain Bank were assessed microscopically by a single examiner blinded to the diagnosis. SVD was assessed by grading perivascular pallor, gliosis, hyaline thickening, and enlargement of perivascular spaces in the white matter underlying the superior frontal and primary motor cortices, basal ganglia, and white matter tracts. A history of vascular risk factors (hypertension, heart disease, diabetes, and cigarette smoking) was obtained. Groups were compared using stepwise multiple regression analysis. There was significantly greater frontal pallor (P = .004) and widening of perivascular spaces in the globus pallidus interna (P = .007) in controls compared with PD. Hyaline thickening and widening of perivascular spaces in the frontal white matter, hyaline thickening in the motor white matter, and widening of perivascular spaces in the caudate nucleus were more common in the control group, but did not reach significance. The prevalence of vascular risk factors and SVD pathology was significantly lower in autopsy-proven PD compared with controls (P = .03) living in the same community. The results of this study support the need for further research in this area.

A comparison of health-care costs involved in treating people with and without Parkinson's disease in Southern Sydney, New South Wales, Australia.

Twelve community-dwelling subjects with Parkinson's disease (PD) and 12 age-matched healthy controls completed a 3-month diary of health-care utilisation in Sydney, Australia. The mean age for the PD group was 71.3 years (SD 5.9, range 62-82 years) versus 73.2 years (SD 6.7, range 63-83 years) for the control group. The mean disease duration of the PD group was 6.8 years (SD 3.6, range 2-14 years). The median Hoehn and Yahr stage was 3 (range 1-3). The mean 3-month total (both related and 'unrelated' to PD) health-care cost for the PD group was significantly higher than that for the 'healthy' control group (1,755 Australian dollars, SD 1,201 versus 413 Australian dollars, SD 515, P=0.001). Medication was the most costly component for both groups (PD 636 Australian dollars, SD 226 versus controls 175 Australian dollars, SD 233, P<0.001) followed by general practitioner or specialist medical expenses (PD 564 Australian dollars, SD 670 versus controls 205 Australian dollars, SD 397, p=0.12) and allied health-care costs (PD 323 Australian dollars, SD 178 versus controls 21 Australian dollars, SD 43, p<0.001). In the PD subgroup, the health-care costs attributed to PD during the 3-month period were significantly higher than health-care costs 'unrelated' to PD (1,202 Australian dollars, SD 820 versus 553 Australian dollars, SD 591, p=0.03). On subgroup analysis, allied health-care costs (related to PD) achieved statistical significance (304 Australian dollars, SD 180 versus 19 Australian dollars, SD 19, p<0.0001), whereas medication and general practitioner or specialist costs did not. In conclusion, we found that the total direct health-care cost of PD for patients with Hoehn and Yahr stage 3 was four times that of age- and sex-matched 'healthy' controls. The estimated annual cost (7,020 Australian dollars per patient) in our patient cohort was comparable to that reported in the United States and Europe.

Positional vomiting due to a thoracic spinal dural arteriovenous fistula. Case report.

The authors report the unique case of a patient with a thoracic spinal dural arteriovenous fistula (DAVF) causing remote brainstem symptoms of positional vomiting and minimal vertigo. Magnetic resonance (MR) imaging of the brain demonstrated high signal abnormality in the medulla, presumably related to venous hypertension, and spinal MR imaging revealed markedly dilated veins along the dorsal aspect of the cord. Spinal angiography confirmed the presence of a thoracic spinal DAVF. Disconnection of the DAVF from the spine resulted in a marked improvement in symptoms and resolution of the preoperative MR imaging-documented abnormalities. The authors highlight the rare syndrome of positional vomiting as a brainstem symptom and conclude that spinal DAVFs should be considered in the differential diagnosis of high signal MR imaging abnormalities localized to the brainstem.

Evoked potentials elicited by stimulation of the lateral and anterior femoral cutaneous nerves in meralgia paresthetica.

Seventy-five consecutive patients with clinical symptoms and signs of meralgia paresthetica underwent bilateral somatosensory evoked potential (SEP) studies involving stimulation of skin areas innervated by the lateral and anterior femoral cutaneous nerves of the thighs. The most common abnormality was an absolute lateral femoral cutaneous SEP latency > 40 ms in 35 patients (47%), followed by an absent response in 14 patients (19%), an absolute latency < 40 ms but amplitude reduction > 50% compared with the contralateral response in 8 patients (11%), and an absolute latency < 40 ms but > 5 ms interside latency difference in 5 patients (7%). Anterior femoral cutaneous SEPs were of value in distinguishing meralgia paresthetica from a proximal lumbar radiculopathy in an additional 4 patients and confirming bilateral meralgia paresthetica in 10 patients.