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Glutamate is the major excitatory neurotransmitter in the central nervous system and, as such, many brain regions, including the basal ganglia, are rich in glutamatergic neurons. The importance of the basal ganglia in the control of voluntary movement has long been recognised, with the effect of dysfunction of the region exemplified by the motor symptoms seen in Parkinson's disease (PD). However, the basal gan-glia and the associated glutamatergic system also play a role in the modulation of emotion, nociception and cognition, dysregulation of which result in some of the non-motor symptoms of PD (depression/anx-iety, pain and cognitive deficits). Thus, while the treatment of PD has traditionally been approached from the perspective of dopaminergic replacement, using agents such as levodopa and dopamine receptor ago-nists, the glutamatergic system offers a novel treatment target for the disease. Safinamide has been approved in over 20 countries globally for fluctuating PD as add-on therapy to levodopa regimens for the management of 'off' episodes. The drug has both dopaminergic and non-dopaminergic pharmacolog-ical effects, the latter including inhibition of abnormal glutamate release. The effect of safinamide on the glutamatergic system might present some advantages over dopamine-based therapies for PD by provid-ing efficacy for motor (levodopa-induced dyskinesia) as well as non-motor (anxiety, mood disorders, pain) symptoms. In this article, we discuss the potential role of glutamatergic inhibition on these symp-toms, using illustrative real-world examples of patients we have treated with safinamide. (c) 2021 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license (http:// creativecommons.org/licenses/by/4.0/).

Ropinirole is a non-ergoline dopamine agonist with medium elimination half time, which has been licensed for the therapy of idiopathic Parkinson syndrome in mono- and add-on therapy for more than 10 years. Since 2008 a prolonged-release formulation has been available in Germany, which can be taken once daily. This formulation results in less plasma level fluctuations compared to the thrice-daily immediate-release formulation enabling smoother dopaminergic therapy with symptomatic efficacy day and night. Ropinirole PR has shown good efficacy and tolerability in controlled trials in monotherapy in early patients as well as in add-on studies in advanced patients. In a head-to-head comparison of both formulations as add-on therapy in advanced patients higher doses were achieved with ropinirole PR accompanied by a higher mean decrease of L-Dopa dose. Under these conditions significantly higher efficacy was observed. The titration regime of ropinirole PR is faster with significant efficacy versus placebo as early as in week 2. Especially in patients with pre-existing Parkinson-related poor sleep quality positive effects on sleep and nocturnal symptoms were shown.

OBJECTIVE To determine whether abnormal orthostatic regulation commonly occurs in patients with Parkinson's disease (PD) and is caused by an abnormal catecholamine release (especially of noradrenaline). PATIENTS AND METHODS Blood pressure and catecholamine concentration were measured after 10-min recumbency and 1, 3, 5, 7 and 9 min after standing up in 46 patients with PD (15 women, 31 men: mean age 64.3 +/- 11.7 years). Results were compared with those in a group of 27 healthy controls (eight women, 19 men; mean age 60.7 +/- 10.8 years). RESULTS Among PD patients there were marked hypotonic circulatory reactions, associated with decreased catecholamine concentration and heart rate adaptation; an abnormal orthostatic regulation occurred in 30 patients. In 22 patients noradrenaline concentration changed by less than 200 pg/ml in the 9th min after standing up, while a decreased hormonal release was noted in only four of the controls, all of whom had normal orthostatic regulation. In PD patients the lowest adrenaline rise was always associated with an extremely high fall in blood pressure. Changes in mean blood pressure correlated positively with the rise in noradrenaline. There was no demonstrable correlation between medication for PD, age of patient and the duration or severity of the disease. CONCLUSION Abnormal orthostatic regulation occurs more frequently in PD than in healthy persons and is associated with changes in noradrenaline release. This suggests multisystem degeneration as a cause of PD.

Ropinirole is a non-ergoline selective D2 dopamine agonist. Its efficacy and safety has been established in several controlled double-blind studies in patients with early and advanced Parkinson's disease. It is assumed that the improvement in the activities of daily living under ropinirole is not only due to the improved motor symptoms but also due to the improvement of non-motor symptoms like symptoms of mood and anxiety. The objective of this post marketing surveillance study was to show that under the conditions of the daily routine in the neurologic practice ropinirole may not only improve motor symptoms, the activity of daily living and complications of the treatment (dystonia, dyskinesia) but also alleviate symptoms of depression and anxiety. A total of 110 neurological practices enrolled 327 patients in early and advanced stages of the disease (139 females, 188-males; mean age: 67 years). They were treated with ropinirole as monotherapy and as adjunctive therapy with l-dopa over a period of 12 - 14 weeks. Selected symptoms of the Unified Parkinson's Disease Rating Scale (UPDRS) part II-IV and symptoms of depression and anxiety were rated by the clinicians. Mood and functional impairment in job, family and social life were rated by the patients using selected items of the Beck Depression Inventory and the Sheehan Disability Scale (SDS). The different subtypes, i. e. the akinetic-rigid, tremor-dominant and the mixed subtype, are described separately. The total UPDRS score at baseline was similar for all three subtypes and there was also a similar improvement in the three groups under ropinirole. Both according to self-rating and to clinician rating the symptoms of depression and anxiety at baseline were more severe in the akinetic-rigid and the mixed subtype compared to the tremor-dominant subtype. The symptoms considerably improved and were reduced by 48 % under therapy with ropinirole. Adverse events were reported by 7.7 % of the patients. The surveillance study has shown that ropinirole may improve not only motor symptoms, activities of daily living and complications of treatment but also symptoms of mood and anxiety.

Copyright: ©2015 Jost WH. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited *Corresponding author: Wolfgang H. Jost, Professor of Neurology, University of Freiburg / Parkinson-Klinik Wolfach, Germany, E-mail: w.jost@parkinson-klinik.de

Autonome Regulationsstörungen beim Parkinsonsyndrom wurden in ihrer Häufigkeit und Ausprägung lange unterschätzt. Mittlerweile ist bekannt, dass sie früh im Krankheitsverlauf auftreten und alle Patienten im Krankheitsverlauf in unterschiedlichem Ausmass betreffen. Deshalb sollten alle Patienten diesbezüglich befragt und untersucht und wo erforderlich auch behandelt werden. Am häufigsten treten kradiovaskuläre, gastrointestinale und urogenitale Symptome auf. Daneben sind aber fast alle Organsysteme betroffen.

Ever since the first description of Parkinson's disease, it has not only been associated with the classical triad of akinesia, rigor and tremor but also with autonomic regulation disorders. However, the studies published on this subject show differing and partly contradictory results. A large number of studies demonstrate a distinct autonomic disorder. On the other hand there are authors who question an affliction of the autonomic nervous system and others who attribute the autonomic disorder to Parkinson specific medication. To make matters worse, the various pathogeneses of Parkinson's syndrome within the patients collectives have not been sufficiently differentiated and nomenclature of the multisystem degeneration was handled in different ways. Taking our examinations of the various autonomic functions and the underlying literature into critical consideration, we come to the conclusion that regulation disorders of the cardiovascular system, gastrointestinal and urinary tract, as well as sweat and thermoregulation are often seen in the idiopathic Parkinson's disease. In our opinion the idiopathic Parkinson's syndrome must be attributed to the multisystem degenerations. Autonomic dysfunction occurs in different intensities in the disease.

We report on a case of a 22-year old primigravida with HELLP syndrome in association with blindness and cerebral sinus thrombosis. The diagnosis of the cerebral sinus thrombosis was based on MRI 1h after delivery. Immediate caesarean section and intensive care treatment led to a complete recovery of the patient.

Neurophysiologic examinations in differential diagnosis of erectile dysfunction comprise electromyogramme of the pelvic floor, pudendal nerve terminal motor latency (PNTML) and evaluation of pudendal somatosensory evoked potentials (SSEP). We focused our interest on comparing diagnostic importance of penile and perianal pudendal nerve SSEP. We examined 20 patients suffering from erectile dysfunction and 20 patients without any manifestation of impotence. The stimulus was administered using penile ring electrodes at the base of the penis (cathode) and distally on the penis shaft (anode), as well as a perianal surface electrode applied at 3 o'clock in lithotomy position and 5 cm laterally on the gluteal skin. The potentials were recorded with intradermal needle electrodes at C(z)-2 cm (different) and F(z) (indifferent). 500 stimuli were averaged for a single tracing. The stimulus strength was set at an average of 3-4 times the stimulus threshold. Cortical latency of P 40 ranged from 39.0 to 45.6 ms (penile) and from 33.6 to 43.2 ms (perianal) in the control group, in the patient group latencies ranged from 38.8 to 51.6 (penile) and 34.0 to 44.8 ms (perianal). In two patients no potential was recordable after perianal stimulation, one patient showed a marked prolongation of the penile response with a normal perianal latency. Penile and perianal latencies of P 40 were significantly prolonged in the patient group compared to the control group (P

The aim of the present study was to evaluate the therapeutic potency of an electrotherapy of striated ischiocavernous muscles in patients with erectile dysfunction.Transcutaneous electrostimulation of striated ischiocavernous muscles by self-adhesive penile or perineal skin electrodes was performed in 48 patients with erectile dysfunction. 6/48 patients (R) responded to intracavernous pharmacotherapy while 42/48 (NR) did not show significant penile rigidity even to intracavernous papaverine/phentolamine/PGE1 triple drug medication.Within the observation time of 3 months, 10/48 patients dropped out. 22/38 patients reported a penile rigidity for sufficient sexual intercourse whereby 3/22 NR required additional intracavernous pharmacotherapy. Penile rigidity could be objectivated by triple drug medicaton in 12/14 NR after ischiocavernous muscle stimulation (EIS) therapy. 5/6 R were treated successfully for premature erection loss. During EIS treatment neither discomfort nor complications could be observed.Transcutaneous electrostimulation of ischiocavernous muscles is a new, noninvasive therapy for the improvement of penile rigidity. The clinical results underline the importance of the striated ischiocavernous muscles for penile rigidity.

Penile sympathic skin response (PSSR) was measured in 20 normal patients and in 46 patients with erectile dysfunction (ED). PSSR could be registered in 80% of normal patients. The latencies were 1,100-1,600 ms. In patients with ED, latencies were 1,240-3,640 ms. A reproducible normal latency of PSSR (1,600 ms) indicates a normal sympathic innervation of the penis. Long latencies (1,800 ms) indicate neuropathy of unmyelinated nerval fibers. The loss of a reproducible answer however allows no exact diagnostic information. PSSR is a useful diagnostic test for detecting neuropathy of unmyelinated nerval fibers as a possible cause of ED.

Bei 67 Patienten mit erektiler Dysfunktion (ED) wurden vergleichend penile sympathische Hautantwort (PSHA) und Corpus-cavernosum-EMG (cc-EMG) untersucht. Durch selektive pharmakologische Blockade des cc-EMG mittels intrakavernoser Injektion von Prostaglandin E1 bei erhaltener PSHA konnte gezeigt werden, das es sich um verschiedene elektrische Phanomene handelt. Die verzogerte Leitungslatenz der PSHA bei Patienten mit Diabetes mellitus und nach radikaler Beckenchirurgie objektivierten einen peripheren Schaden des sympathischen Nervensystems besser als das cc-EMG. Die Erfassung von spontanen Salvenpotentialen im cc-EMG bei Ruckenmarksverletzungen belegten eine gestorte sympathisch-parasympathische Synchronisation als mogliche Ursache einer ED. Beide Verfahren stellen in Kombination bei limitierter Aussage einen ersten Schritt zur Erfassung einer penilen autonomen Neuropathie dar. A comparision between penile sympathic skin response (PSSR) and corpus cavernosum-EMG (cc-EMG) was done in 67 patients. Spontaneous potentials of cc-EMG were blocked by intracavernous injection of PGE1 whereas PSSR was not influenced, demonstrating 2 electrical phenomena. Prolonged latencies in PSSR in patients with diabetes mellitus and radical pelvic surgery were favorable for PSSR in detecting peripheral nerve damage. In lumbar spine damage, bursts as a sign of a disturbed sympathic-parasympathic coordination could only be detected by cc-EMG. Both examinations in combination are a first step for a limited access to penile autonomic innervation in erectile dysfunction.