Therapeutic use of medical Cannabis in neurological diseases: a clinical update.

The use of medical Cannabis has increased in recent years due to changing legal circumstances in many countries. Approval exists only for a few neurological conditions such as rare forms of epilepsy or spasticity in multiple sclerosis. Beyond that, however, medical Cannabis is used for a wide range of neurological conditions and symptoms. In Germany, in parallel with new legislation that has simplified the prescription of medical Cannabis, an accompanying survey has been implemented for which initial data are now available. In this context, our review provides an overview of the evidence for the therapeutic use of medical Cannabis in neurology, the potential benefits, and side effects.

Combined Short-Pulse and Directional Deep Brain Stimulation of the Thalamic Ventral Intermediate Area for Essential Tremor.

OBJECTIVE: Novel deep brain stimulation (DBS) systems allow directional and short-pulse stimulation to potentially improve symptoms and reduce side effects. The aim of this study was to investigate the effect of short-pulse and directional stimulation, in addition to a combination of both, in the ventral intermediate thalamus (VIM)/posterior subthalamic area (PSA) on tremor and stimulation-induced side effects in patients with essential tremor. MATERIALS AND METHODS: We recruited 11 patients with essential tremor and VIM/PSA-DBS. Tremor severity (Fahn-Tolosa-Marin), ataxia (International Cooperative Ataxia Rating Scale), and paresthesia (visual analog scale) were assessed with conventional omnidirectional and directional stimulation with pulse width of 60 µs and 30 µs. RESULTS: All stimulation conditions reduced tremor. The best directional stimulation with 60 µs reduced more tremor than did most other stimulation settings. The best directional stimulation, regardless of pulse width, effectively reduced stimulation-induced ataxia compared with the conventional stimulation (ring 60 µs) or worst directional stimulation with 60 µs. All new stimulation modes reduced occurrence of paresthesia, but only the best directional stimulation with 30 µs attenuated paresthesia compared with the conventional stimulation (ring 60 µs) or worst directional stimulation with 60 µs. The best directional stimulation with 30 µs reduced tremor, ataxia, and paresthesia compared with conventional stimulation in most patients. Correlation analyses indicated that more anterior stimulation sites are associated with stronger ataxia reduction with directional 30 µs than with conventional 60 µs stimulation. CONCLUSION: Directional and short-pulse stimulation, and a combination of both, revealed beneficial effects on stimulation-induced adverse effects.

Short pulse and directional thalamic deep brain stimulation have differential effects in parkinsonian and essential tremor.

The aim of this study was to assess the effects of novel stimulation algorithms of deep brain stimulation (short pulse and directional stimulation) in the ventrointermediate thalamus and posterior subthalamic area (VIM/PSA-DBS) on tremor in Parkinson's disease (PD) and to compare the effects with those in essential tremor (ET). We recruited six PD patients (70.8 ± 10.4 years) and seven ET patients (64.4 ± 9.9 years) with implanted VIM/PSA-DBS in a stable treatment condition (> 3 months postoperatively). Tremor severity and ataxia were assessed in four different stimulation conditions in a randomized order: DBS switched off (STIM OFF), omnidirectional stimulation with 60 µs (oDBS60), omnidirectional stimulation with 30 µs (oDBS30), directional stimulation at the best segment with 60 µs (dDBS60). In both patient groups, all three DBS stimulation modes reduced the total tremor score compared to STIM OFF, whereas stimulation-induced ataxia was reduced by oDBS30 and partially by dDBS60 compared to oDBS60. Tremor reduction was more pronounced in PD than in ET due to a limited DBS effect on intention and action-specific drawing tremor in ET. In PD and ET tremor, short pulse or directional VIM/PSA-DBS is an effective and well tolerated therapeutic option.Trial registration: The study was registered in the DRKS (ID DRKS00025329, 18.05.2021, German Clinical Trials Register, DRKS-Deutsches Register Klinischer Studien).

Comparison of Montreal cognitive assessment and Mattis dementia rating scale in the preoperative evaluation of subthalamic stimulation in Parkinson's disease.

INTRODUCTION: The preoperative evaluation of Parkinson's Disease (PD) patients for subthalamic nucleus deep brain stimulation (STN-DBS) includes the assessment of the neuropsychological status of the patient. A widely used preoperative test is the Mattis Dementia rating scale (MDRS). However, the Montreal cognitive assessment (MoCA) has also been proven to be a sensitive, time-sparing tool with high diagnostic validity in PD. We evaluate the utility of the MoCA as a preoperative screening test for PD patients undergoing bilateral STN-DBS. METHODS: In this single-centre, retrospective study, we analysed pre- and postoperative assessments of MoCA, MDRS, Movement disorder society-Unified PD Rating Scale-motor examination, PD Questionnaire-39 and levodopa equivalent daily dose. Longitudinal outcome changes were analysed using paired t-test, Pearson's correlation coefficient, linear regression and CHAID (chi-square automatic interaction detector) regression tree model. RESULTS: Clinical motor and cognitive scores of 59 patients (61.05±7.73 years, 24 females) were analysed. The MoCA, but not the MDRS, identified significant postoperative cognitive decline in PD patients undergoing STN-DBS. The preoperative MoCA score correlated with postoperative quality of life improvement, whereas the MDRS did not. PD patients with a MoCA score ≤ 23 points had a significant decline of quality of life after DBS surgery compared to patients > 23 points. CONCLUSION: This study identifies the MoCA as an alternative test within the preoperative evaluation of PD patients for the detection of neuropsychological deficits and prediction of the postoperative improvement of quality of life.

Thalamic short pulse stimulation diminishes adverse effects in essential tremor patients.

OBJECTIVE: To investigate the effect of directional current steering and short pulse stimulation in the ventral intermediate thalamic nucleus (VIM) on stimulation-induced side effects in patients with essential tremor. METHODS: We recruited 8 patients with essential tremor in a stable postoperative condition (>3 months after electrode implantation of deep brain stimulation [DBS] electrodes) with segmented contacts implanted in the VIM. Tremor severity on acute stimulation was assessed by the Fahn-Tolosa-Marin Tremor Rating Scale. Cerebellar impairment was evaluated with the International Cooperative Ataxia Rating Scale. Patients rated paresthesia intensity with a visual analog scale. RESULTS: In all patients, tremor was reduced to the same extent by VIM stimulation regardless of pulse width using energy dose-equivalent amplitudes. Short pulse stimulation diminished stimulation-induced ataxia of the upper extremities and paresthesia compared with conventional parameters. Directional steering with monopolar stimulation of single segments successfully suppressed tremor but also induced ataxia. No differences in adverse effects were found between single-segment stimulation conditions. CONCLUSION: These proof-of-principle findings provide evidence that acute short pulse stimulation is superior to directional steering in the subthalamic area to decrease stimulation-induced side effects while preserving tremor suppression effects in patients with tremor. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that for patients with tremor with thalamic DBS, acute short pulse stimulation reduces adverse effects, while directional steering does not provide a generalizable benefit regarding adverse effects.

[Cannabis in Parkinson's Disease: Hype or help?] / Cannabis bei Parkinson ­ Hype oder Heilmittel?

Cannabis buds and extracts as well as synthetic cannabinoids have been available on prescription to patients with severe diseases since March 2017, with the costs covered by health insurance companies.The prescription of medical marihuana is not restricted to specific symptoms and is therefore also valid for patients with Parkinson's disease. From a legal perspective, patients who are seriously ill even have the right to be treated with cannabis if standard treatment methods are unsuccessful or result in unbearable side effects. This also applies even if only a slight chance of noticeable improvement is predicted as a result of the cannabis treatment.Bearing this in mind and due to an intense media coverage of this topic, more and more patients with Parkinson's disease are requesting cannabis prescription, which is a challenging situation to their neurologists.This article provides an overview of the various cannabis products that can be prescribed, the different modes of administration and the available literature regarding motor- and non-motor symptoms in Parkinson's disease. Furthermore, the authors state their opinion on which indications cannabinoids could be useful in treating patients with Parkinson's disease or in which situation the patient could or even should be prescribed cannabinoids. Additionally, this article presents practical recommendations for the prescription of cannabinoids and patient counseling, e. g., on the effects of medical marijuana on driving capacity.

Pain in Parkinson disease: a cross-sectional survey of its prevalence, specifics, and therapy.

We aimed to evaluate prevalence, phenotype, and therapeutic realities of pain in patients with Parkinson disease (PD). Therefore, we assessed 181 outpatients with PD using a cross-sectional approach applying the German Pain Questionaire (DSF), the PainDetect, and a self-developed Parkinson Disease Pain Questionaire (UPDPQ) covering detailed therapeutic aspects. Furthermore, we investigated the association between pain and PD-disease characteristics, quality of life (PDQ-39), depression, and anxiety (HADS-D, HADS-A). Overall, prevalence of pain was high (95.4%); 91.1% suffered from chronic pain, but in only 22.3% of them, pain disorder was diagnosed. Pain impaired everyday-life moderately to very severely in 48.4% of patients and was the most distressing symptom in 10.2% of all patients. Pain was localized mainly in the back (71.4%) or joints (52.4%), frequently occurred as pain attacks (79%) but appeared with neuropathic character in only 15.3% of patients. Most patients (74.2%) received some kind of pain treatment, mainly provided by orthopedists (62.0%) or general practitioners (50.0%). Physiotherapy (61.3%), pain killers (54.4%), or massage (35.5%) were the most frequent therapeutic measures. Rehabilitative therapy (96.3%) and physiotherapy (89.5%) were rated as most effective, but with vastly temporary effects. 53.3% of patients attributed PD as the main cause for their pain, but only 33.6% found relief from anti-parkinsonian drugs. High levels of pain were associated with higher scores of depression and anxiety, and lower quality of life. Results suggest that pain in PD is frequent, complex, and quality-of-life-impairing but under-diagnosed and unsystematically treated and indicate need to systematically investigate pathophysiology-based treatment strategies.