Brainstem raphe alterations in TCS

Depression and apathy can both be present in patients with Parkinson's disease (PD) while e. g., essential tremor (ET) patients mostly only report depressive symptoms. In PD, depression has been linked with brainstem raphe (BR) signal alterations in transcranial sonography (TCS) but apathy has not been evaluated in such terms as a putative biomarker. Furthermore, the BR has only been investigated using a singular axial TCS examination plane, although coronal TCS examination allows a much more accurate evaluation of the craniocaudal formation of serotonergic raphe structures in the midbrain area. The objective of this study was to investigate the value of coronal TCS examination for the detection of BR signal alterations and clinically correlate it to apathy in patients with PD, ET and healthy controls (HC). We prospectively included PD patients ($\it n$ = 31), ET patients ($\it n$ = 16), and HC ($\it n$ = 16). All were examined by TCS in the axial and coronal plane with focus on BR signal alterations. LARS and BDI-II scores were conducted to assess apathic and depressive symptoms in the study population. In a detailed analysis we found that the correlation of coronal and axial TCS alterations of BR was very high (rho = 0.950, p < 0.001). BR signal alterations were more frequent in PD patients than in ET patients and HC, while it was not different between ET patients and HC. In the PD patient group, BDI-II and LARS scores were negatively correlated to BR signal changes in TCS in a significant manner (BDI-II and axial BR: $\it p$ = 0.019; BDI-II and coronal BR: $\it p$ = 0.011; LARS and axial BR: $\it p$ = 0.017; LARS and coronal BR: $\it p$ = 0.023). Together in this brainstem ultrasound study we find a significant association of BR signal alterations with clinically evident apathy and depression in patients with PD. Therefore, TCS might enable the identification of a subgroup of PD patients which are at higher risk to suffer from or to develop depression or apathy

Brainstem raphe alterations in TCS

Depression and apathy can both be present in patients with Parkinson's disease (PD) while e. g., essential tremor (ET) patients mostly only report depressive symptoms. In PD, depression has been linked with brainstem raphe (BR) signal alterations in transcranial sonography (TCS) but apathy has not been evaluated in such terms as a putative biomarker. Furthermore, the BR has only been investigated using a singular axial TCS examination plane, although coronal TCS examination allows a much more accurate evaluation of the craniocaudal formation of serotonergic raphe structures in the midbrain area. The objective of this study was to investigate the value of coronal TCS examination for the detection of BR signal alterations and clinically correlate it to apathy in patients with PD, ET and healthy controls (HC). We prospectively included PD patients ($\it {n}$ = 31), ET patients ($\it {n}$ = 16), and HC ($\it {n}$ = 16). All were examined by TCS in the axial and coronal plane with focus on BR signal alterations. LARS and BDI-II scores were conducted to assess apathic and depressive symptoms in the study population. In a detailed analysis we found that the correlation of coronal and axial TCS alterations of BR was very high (rho = 0.950, $\it {p}$ < 0.001). BR signal alterations were more frequent in PD patients than in ET patients and HC, while it was not different between ET patients and HC. In the PD patient group, BDI-II and LARS scores were negatively correlated to BR signal changes in TCS in a significant manner (BDI-II and axial BR: $\it {p}$ = 0.019; BDI-II and coronal BR: $\it {p}$ = 0.011; LARS and axial BR: $\it {p}$ = 0.017; LARS and coronal BR: $\it {p}$ = 0.023). Together in this brainstem ultrasound study we find a significant association of BR signal alterations with clinically evident apathy and depression in patients with PD. Therefore, TCS might enable the identification of a subgroup of PD patients which are at higher risk to suffer from or to develop depression or apathy

Successful therapy with rituximab in three patients with probable neurosarcoidosis

$\bf Background:$ Neurosarcoidosis occurs in about 5–15% of patients with sarcoidosis. Therapy with corticosteroids is generally accepted as the first-line medication, followed by various immunomodulating and cytotoxic agents or combined therapy. However, some patients show an unsatisfactory outcome or have adverse events and require novel treatment strategies. $\bf Methods:$ We describe three patients with systemic sarcoidosis and central nervous system involvement who received CD20-targeted B-cell depletion with rituximab. $\bf Results:$ Treatment with rituximab was well tolerated and followed by marked remission in patients nonresponsive to other immunosuppressive agents. $\bf Conclusion:$ Rituximab may be used for patients with neurosarcoidosis who are nonresponsive to established treatment regimes

Hospitalization rates and comorbidities in patients with progressive supranuclear palsy in Germany from 2010 to 2017

Progressive supranuclear palsy (PSP) belongs to the disease spectrum of Parkinsonian syndromes. Due to the chronic and progressive neurodegenerative course of the disease, PSP patients often have to be hospitalized to undergo diagnostic and therapeutic measures. The dynamics and characteristics of PSP inpatient treatment in Germany have not been investigated thus far. The current study analyzed trends of inpatient treatment in Germany for the years 2010–2017 based on the German DRG statistics ("diagnostic-related groups") in the category G23.- (other degenerative diseases of the basal ganglia) and with special focus on PSP (G23.1). Inpatient case numbers of the G23.- category comprised a total of 21,196 patients from 2010–2017, whereas the PSP subcategory (G23.1) amounted to 10,663 cases. In the analyzed time period, PSP patient numbers constantly increased from 963 in 2010 to 1780 in 2017 with yearly growth rates of up to 20%. Similar trends were observed for other Parkinsonian syndromes such as multiple system atrophy (MSA). Differentiating PSP inpatients by gender demonstrated a higher proportion of males (55–60%) in comparison to female patients for the entire observation period. The average age of hospitalized PSP patients over these years was between 72.3 and 73.4 years without relevant differences for gender. The most common comorbidities consisted of cardiovascular, neurological, muscular and urological disorders. In summary, the analysis demonstrates that PSP patients are increasingly hospitalized in Germany and the current concepts of stationary care have to differentiate standard practices for Parkinson’s disease (PD) to also address the needs of patients with PSP and other Parkinsonian syndromes

Diagnostic value of the impairment of olfaction in Parkinson's disease

$\it Background$ Olfactory impairment is increasingly recognized as an early symptom in the development of Parkinson's disease. Testing olfactory function is a non-invasive method but can be time-consuming which restricts its application in clinical settings and epidemiological studies. Here, we investigate odor identification as a supportive diagnostic tool for Parkinson's disease and estimate the performance of odor subsets to allow a more rapid testing of olfactory impairment. $\textit {Methodology/Principal Findings}$ Odor identification was assessed with 16 Sniffin' sticks in 148 Parkinson patients and 148 healthy controls. Risks of olfactory impairment were estimated with proportional odds models. Random forests were applied to classify Parkinson and non-Parkinson patients. Parkinson patients were rarely normosmic (identification of more than 12 odors; 16.8%) and identified on average seven odors whereas the reference group identified 12 odors and showed a higher prevalence of normosmy (31.1%). Parkinson patients with rigidity dominance had a twofold greater prevalence of olfactory impairment. Disease severity was associated with impairment of odor identification (per score point of the Hoehn and Yahr rating OR 1.87, 95% CI 1.26–2.77). Age-related impairment of olfaction showed a steeper gradient in Parkinson patients. $\textit {Coffee, peppermint}$, and $\it anise$ showed the largest difference in odor identification between Parkinson patients and controls. Random forests estimated a misclassification rate of 22.4% when comparing Parkinson patients with healthy controls using all 16 odors. A similar rate (23.8%) was observed when only the three aforementioned odors were applied. $\textit {Conclusions/Significance}$ Our findings indicate that testing odor identification can be a supportive diagnostic tool for Parkinson's disease. The application of only three odors performed well in discriminating Parkinson patients from controls, which can facilitate a wider application of this method as a point-of-care test

Highly immunoreactive IgG antibodies directed against a set of twenty human proteins in the sera of patients with amyotrophic lateral sclerosis identified by protein array

Amyotrophic lateral sclerosis (ALS), the most common adult-onset motor neuron disorder, is characterized by the progressive and selective loss of upper and lower motor neurons. Diagnosis of this disorder is based on clinical assessment, and the average survival time is less than 3 years. Injections of IgG from ALS patients into mice are known to specifically mark motor neurons. Moreover, IgG has been found in upper and lower motor neurons in ALS patients. These results led us to perform a case-control study using human protein microarrays to identify the antibody profiles of serum samples from 20 ALS patients and 20 healthy controls. We demonstrated high levels of 20 IgG antibodies that distinguished the patients from the controls. These findings suggest that a panel of antibodies may serve as a potential diagnostic biomarker for ALS