Discordance Between Perceptions and Experience of Lumbar Puncture: A Prospective Study.

Background and Objectives: Novel diagnostic techniques and neurologic biomarkers have greatly expanded clinical indications for CSF studies. CSF is most commonly obtained via lumbar puncture (LP). Although it is generally believed that LPs are well tolerated, there is a lack of supportive data for this claim, and patients anticipate LP to be painful. The objective of this study was to prospectively investigate discordance between patient perception and tolerability of LP. Methods: Adult patients were surveyed before and after LP regarding their perceptions and experience of LP. Physician perceptions were gathered through a web-based survey. Relative risk and Spearman correlation were used to assess the relationship between responses. Paired binomial and paired ordinal responses were compared by McNemar and paired Wilcoxon rank-sum tests. Results: A total of 178 patients completed the surveys. About half of the patients (58%) reported anxiety pre-LP, at median 3.0 of 10. Physicians overpredicted patients' pre-LP anxiety (median score 5.0, p < 0.001). Experienced pain was significantly less than predicted pain (median scores 0 and 3.0, respectively, p < 0.001). Patients who predicted pain were more likely to report pain from LP (relative risk [RR] 1.3). Predicting pain was also correlated with anxiety before LP (p < 0.001). Discussion: LP was generally well tolerated. The majority of patients experienced minimal pain. Anticipation of pain was correlated with both feeling anxious and experiencing pain. The results of this study can be used to reassure patients and providers that LP is indeed not as painful as imagined, which may both reduce pre-LP anxiety and improve LP tolerability.

A Young Adult with White Matter Changes and Recurrent Stroke Symptoms.

White matter changes on MRI can be a diagnostic puzzle as a large group of inflammatory, autoimmune, infectious, and neoplastic conditions can present in this way. An otherwise healthy 36-year-old male presented with his second episode of unilateral weakness, the first episode occurring five years previously. He did not have sensory or cerebellar symptoms with the current or previous episode. He reported that his grandfather, father, two of his aunts, and an uncle had multiple sclerosis (MS), dying in their 40s-50s from their disease. The MRI during his first hospitalization revealed acute ischemia as well as diffuse white matter hyperintensities. The current MRI revealed new ischemic changes as well as progression of the white matter hyperintensities with notable temporal lobe involvement. While small vessel disease and multiple sclerosis can present similarly, the history of stroke, lesion distribution, and family history suggested an alternative diagnosis. Due to high clinical suspicion, genetic testing was performed for CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy) and confirmed the diagnosis. This case report describes the approach to the adult with white matter changes and describes the typical presentation and findings of CADASIL, the most common heritable cause of stroke and vascular dementia in adults.

Interval timing and midfrontal delta oscillations are impaired in Parkinson's disease patients with freezing of gait.

Gait abnormalities and cognitive dysfunction are common in patients with Parkinson's disease (PD) and get worse with disease progression. Recent evidence has suggested a strong relationship between gait abnormalities and cognitive dysfunction in PD patients and impaired cognitive control could be one of the causes for abnormal gait patterns. However, the pathophysiological mechanisms of cognitive dysfunction in PD patients with gait problems are unclear. Here, we collected scalp electroencephalography (EEG) signals during a 7-s interval timing task to investigate the cortical mechanisms of cognitive dysfunction in PD patients with (PDFOG +, n = 34) and without (PDFOG-, n = 37) freezing of gait, as well as control subjects (n = 37). Results showed that the PDFOG + group exhibited the lowest maximum response density at around 7 s compared to PDFOG- and control groups, and this response density peak correlated with gait abnormalities as measured by FOG scores. EEG data demonstrated that PDFOG + had decreased midfrontal delta-band power at the onset of the target cue, which was also correlated with maximum response density and FOG scores. In addition, our classifier performed better at discriminating PDFOG + from PDFOG- and controls with an area under the curve of 0.93 when midfrontal delta power was chosen as a feature. These findings suggest that abnormal midfrontal activity in PDFOG + is related to cognitive dysfunction and describe the mechanistic relationship between cognitive and gait functions in PDFOG + . Overall, these results could advance the development of novel biosignatures and brain stimulation approaches for PDFOG + .

Color discrimination errors associate with axial motor impairments in Parkinson's disease.

BACKGROUND: Visual function deficits are more common in imbalance-predominant compared to tremor-predominant PD suggesting a pathophysiological role of impaired visual functions in axial motor impairments. OBJECTIVE: To investigate the relationship between changes in color discrimination and motor impairments in PD while accounting for cognitive or other confounder factors. METHODS: PD subjects (n=49, age 66.7±8.3 years; Hoehn & Yahr stage 2.6±0.6) completed color discrimination assessment using the Farnsworth-Munsell 100 Hue Color Vision Test, neuropsychological, motor assessments and [11C]dihydrotetrabenazine vesicular monoamine transporter type 2 PET imaging. MDS-UPDRS sub-scores for cardinal motor features were computed. Timed up and go mobility and walking tests were assessed in 48 subjects. RESULTS: Bivariate correlation coefficients between color discrimination and motor variables were significant only for the Timed up and go (RS=0.44, P=0.0018) and the MDS-UPDRS axial motor scores (RS=0.38, P=0.0068). Multiple regression confounder analysis using the Timed up and go as outcome parameter showed a significant total model (F(5,43)= 7.3, P<0.0001) with significant regressor effects for color discrimination (standardized ß=0.32, t=2.6, P=0.012), global cognitive Z-score (ß=-0.33, t=-2.5, P=0.018), duration of disease (ß=0.26, t=1.8, P=0.038), but not for age or striatal dopaminergic binding. The color discrimination test was also a significant independent regressor in the MDS-UPDRS axial motor model (standardized ß=0.29, t=2.4, P=0.022; total model t(5,43)= 6.4, P=0.0002). CONCLUSIONS: Color discrimination errors associate with axial motor features in PD independent of cognitive deficits, nigrostriatal dopaminergic denervation, and other confounder variables. These findings may reflect shared pathophysiology between color discrimination visual impairments and axial motor burden in PD.

Huntington's Disease-Update on Treatments.

Huntington's disease (HD) is an autosomal dominantly inherited neurodegenerative disease characterized by progressive motor, behavioral, and cognitive decline, ending in death. Despite the discovery of the underlying genetic mutation more than 20 years ago, treatment remains focused on symptomatic management. Chorea, the most recognizable symptom, responds to medication that reduces dopaminergic neurotransmission. Psychiatric symptoms such as depression and anxiety may also respond well to symptomatic therapies. Unfortunately, many other symptoms do not respond to current treatments. Furthermore, high-quality evidence for treatment of HD in general remains limited. To date, there has been minimal success with identifying a disease-modifying therapy based upon molecular models. However, one of the emerging gene silencing techniques may provide a breakthrough in treating this devastating disease.