Educational attainment and motor burden in advanced Parkinson's disease - The emerging role of education in motor reserve.

OBJECTIVE: To explore the relationship of motor burden and educational attainment in patients with advanced stage PD. MATERIALS AND METHODS: We included 102 consecutive patients who underwent a complete evaluation for DBS surgery, including detailed neuropsychological testing and UPDRSIII in a standardized Levodopa challenge. Years of education (YoE) were calculated as the highest grade attained in secondary school plus years for post-secondary training. RESULTS: The OFF medication UPDRS-III score was associated with YoE (p=0.006; t=-2.82) and age (p=0.007; t=-2.75) in our multivariable linear regression model even while including disease duration (p=0.8; t=0.21), presence of mild cognitive impairment (MCI) (p=0.9; t=0.16) or current IQ (p=0.2; t=1.25) as additional covariables. In a subgroup of 60 patients two years after DBS, the ON/ON UPDRS score was associated with YoE (p=0.01; t=-2.42) and diagnosis of PD dementia (p=0.05, t=1.95), while age (p=0.08, t=1.75), disease duration (p=0.6t=0.48) and LEDD (p=0.3; t=1.05) showed no significant association to ON/ON UPDRS score. CONCLUSIONS: We found an inverse correlation between years of education and lower (better) UPDRS -III motor score after adjusting for important covariables. Education may lead to an increased ability to compensate disturbances in basal ganglia circuits affecting not only for cognitive, but also for motor aspects of PD. Thus, educational attainment may play an important role in the concept of motor reserve.

Intraoperative clinical testing overestimates the therapeutic window of the permanent DBS electrode in the subthalamic nucleus.

BACKGROUND: Intraoperative test stimulation is established to optimize target localization in STN DBS, but requires a time-consuming awake surgery in off-medication state. The aim of this study was to compare the thresholds of stimulation-induced effects of test stimulation and the permanent electrode. METHODS: Fifty-nine PD patients receiving bilateral STN DBS were clinically examined with stepwise increasing monopolar stimulation during surgery and DBS programming at matched stimulation depths. Thresholds of therapeutic and side effects were obtained from standardized examination protocols. RESULTS: Postoperative stimulation via the permanent electrode caused side effects at a significantly lower threshold than predicted during intraoperative test stimulation (P < 0.001); whereas sufficient therapeutic effects were achieved at significantly higher thresholds (P < 0.001). CONCLUSIONS: Intraoperative testing may lead to an overestimation of the therapeutic window. The two different electrodes lead to distinct spreading of the electric field in the STN and surrounding tissues that causes different volume of tissue activated (VTA). Clinicians involved in DBS surgery and programming should be aware of the differences in both stimulation settings, concerning electrodes geometry, stimulation modes as well as the impact of time. Therapeutic and side effects of permanent stimulation are not predictable by intraoperative test stimulation. Test stimulation may be an orientating test for very low thresholds of side effects instead.

Saccadic Impairments in Patients with the Norrbottnian Form of Gaucher's Disease Type 3.

BACKGROUND: Chronic neuronopathic Gaucher's disease type 3 (GD3) is relatively frequent in northern Sweden. Besides multiple other neurological symptoms, horizontal gaze palsy or oculomotor apraxia is common in GD3. OBJECTIVE: To characterize the saccades in patients with Norrbottnian GD3 with respect to their neurological and cognitive status using a computer-based eye-tracking technique. METHODS: Horizontal and vertical reflexive saccades as well as antisaccades of nine GD3 patients [4M/5F; 41.1 ± 11.0 years; modified severity scoring tool (mSST): 9.3 ± 5.4; Montreal Cognitive Assessment (MoCA): 24.0 ± 4.2] and age-matched controls were analyzed using EyeBrain T2, a head-mounted binocular eye tracker. Systematic clinical assessment included the mSST, a valid tool for monitoring the neurological progression in GD3 and MoCA. RESULTS: In Norrbottnian GD3 patients, gain, peak, and average velocity (107.5°/s ± 41.8 vs. 283.9°/s ± 17.0; p = 0.0009) of horizontal saccades were reduced compared to healthy controls (HCs). Regarding vertical saccades, only the average velocity of downward saccades was decreased (128.6°/s ± 63.4 vs. 244.1°/s ± 50.8; p = 0.004). Vertical and horizontal saccadic latencies were increased (294.3 ms ± 37.0 vs. 236.5 ms ± 22.4; p = 0.005) and the latency of horizontal reflexive saccades was correlated with the mSST score (R2 = 0.80; p = 0.003). The latency of antisaccades showed association to MoCA score (R2 = 0.70; p = 0.009). GD3 patients made more errors in the antisaccade task (41.5 ± 27.6% vs. 5.2 ± 5.8%; p = 0.005), and the error rate tended to correlate with the cognitive function measured in MoCA score (p = 0.06). CONCLUSION: The mean age of 41 years of our GD3 cohort reflects the increased life expectancy of patients in the Norrbottnian area compared to other GD3 cohorts. Marked impairment of horizontal saccades was evident in all patients, whereas vertical saccades showed distinct impairment of downward velocity. Latency of reflexive saccades was associated with the severity of neurological symptoms. Increased latency and error rate in the antisaccade task were linked to cognitive impairment. The assessment of saccades provides markers for neurological and neuropsychological involvement in Norrbottnian GD3.

Suspected Perinatal Depression Revealed to be Hereditary Diffuse Leukoencephalopathy with Spheroids.

Early motor symptoms of neurodegenerative diseases often appear in combination with psychiatric symptoms, such as depression or personality changes, and are in danger of being misdiagnosed as psychogenic in young patients. We present the case of a 32-year-old woman who presented with rapid-onset depression, followed by a hypokinetic movement disorder and cognitive decline during pregnancy. Genetic testing revealed a mutation in the colony-stimulating factor 1 receptor gene, which led to the diagnosis of hereditary diffuse leukoencephalopathy with spheroids. Hereditary diffuse leukoencephalopathy with spheroids (HDLS) is probably an under-recognized disease. HDLS should be considered in patients with rapidly progressing parkinsonian symptoms and dementia accompanied by white matter lesions.

Benefit of ELISpot in early diagnosis of tuberculous meningoencephalitis: Case report and literature review.

Tuberculous meningitis and meningoencephalitis are rare and dangerous complications of infections with mycobacteria-complex. Usually these are complications of systemic florid infection with Mycobacterium (M.) tuberculosis. They are most often seen in immune compromised patients. The confirmation of diagnosis can be elaborate and delayed due to long-term culture requirements for M. tuberculosis. We present a female patient, without history of immunosuppression, who was diagnosed with tuberculous meningoencephalitis using ELISpot to detect immune reactivity against mycobacterial antigens with lymphocytes from cerebrospinal fluid (CSF). ELISpot with CSF derived lymphocytes seems to be an appropriate method to diagnose tuberculous meningitis and meningoencephalitis and to make therapeutic decisions easier and earlier in atypical cases of infection with M. tuberculosis.