Thomas Müller

Saint Joseph Hospital Berlin · Neurology

Emerging studies suggest a correlation between elevated plasma homocysteine (hcy) levels and the risk of atherosclerosis, vascular disorders, and neurodegenerative diseases, including Parkinson's disease (PD). This narrative review delves into the intricate relationships between Hcy, vitamin B metabolites, dopamine-substituting compounds, and vario...

Background: Intravenous application of amantadine sulfate induces a rapid improvement of motor behavior in patients with Parkinson disease. Objectives: To determine efficacy of daily infusion of 200 mg amantadine sulfate on scored motor symptoms and performance of standardized movement sequences with components of low and high cognitive efforts....

A biomarker for declined methylation capacity is elevation of homocysteine levels. They increase the risk for onset of vascular disease and contribute to progression of chronic neurodegeneration and aging. This narrative review discusses associations between homocysteine, consumption of methyl group-donating vitamins and impact on disease-generatin...

Dopamine agonists are an important component of Parkinson's therapy. When weighing up the various therapy options, therapy with levodopa has recently been increasingly preferred due to its stronger efficacy and the ostensibly lower rate of side effects. The advantage of the lower incidence of motor complications during therapy with dopamine agonist...

Introduction: Adenosine antagonism, i.e. of the A2A receptor, improves dopamine sensitive motor behaviour in patients with Parkinson's disease with oral levodopa associated motor complications. Only the xanthine derivative istradefylline is currently approved in Japan und in the US. This compound easily crosses the blood brain barrier and shows hi...

Introduction: The aminoadamantanes amantadine and memantine are well known. They mainly act as N-methyl-D-aspartate antagonists. Areas covered: The antiviral drug amantadine moderately ameliorates impaired motor behavior in patients with Parkinson's disease. Memantine provides beneficial effects on memory function in patients with advanced Alzhe...

This editorial discusses the current standstill in research in Parkinson’s disease from a clinician’s point of view [...]

The N-methyl-D-Aspartate receptor antagonist memantine with its less popular monoamine reuptake-inhibiting properties provides beneficial effects in patients with advanced Alzheimer’s disease on an acetylcholine esterase inhibitor treatment regimen. Memantine counteracts deficits of monoamine neurotransmission with associated common clinical sympto...

Compounds, which inhibit enzyme activity of catechol-O-methyltransferease, are commonly employed in combination with levodopa/dopadecarboxylase inhibitor formulations in patients with Parkinson’s disease. They ameliorate wearing-off symptoms by prolongation of the peripheral half-life of levodopa, increase of the peripheral levodopa bioavailability...

Antiparkinsonian activity of amantadine was first described in 1969 and was confirmed by several trials in later years. The improvement of parkinsonian symptoms is mild. However, in patients with motor fluctuations, clear reduction of dyskinesia could be observed. A possible neuroprotective impact is still under discussion, but lacking evidence. Th...

Management of Parkinson’s disease is complex and involves several pharmacologic principles. It is essential to understand the peculiarities of each pharmacologic compound in terms of pharmacology and biochemistry. This is the precondition to perform a personalized therapy of Parkinson’s disease. Efficacy and safety of drugs is different in each pat...

Previous trials describe a decrease of vitamin D levels in patients with Parkinson's disease and relationships to clinical disease severity. This case control study found higher but not significant 25-OH-vitamin D plasma levels in patients with Parkinson's disease compared with age- and sex-matched controls and no associations to clinical parameter...

Motor behaviour in patients with Parkinson’s disease is determined with instrumental tests and rating procedures. Results mirror impairment of an individual patient. Objectives were to determine the associations between two kinds of motion series and rating scores in previously untreated 64 patients and to compare outcomes to controls. The line tra...

The catechol-O-methyltransferase inhibitors entacapone and opicapone prolong the efficacy of conventional oral levodopa/dopa decarboxylase inhibitor formulations through an increase in levodopa plasma bioavailability. Catechol-O-methyltransferase inhibitors influence the homocysteine metabolism associated with levodopa/dopa decarboxylase applicatio...

The clinical presentation of Parkinson’s disease (PD) is both complex and heterogeneous, and its precise classification often requires an intensive work-up. The differential diagnosis, assessment of disease progression, evaluation of therapeutic responses, or identification of PD subtypes frequently remains uncertain from a clinical point of view....

Introduction: Current research paradigms on biomarkers for chronic neurodegenerative diseases, such as Parkinson's disease, focus on the identification of reliable, easy-to-apply tools for diagnostic screening and progression assessment. Areas covered: This perspective discusses possible misconceptions of biomarker research in chronic neurodegen...

Background Immediate Release (IR) amantadine has been used for treatment of levodopa induced dyskinesia (LID). The immediate-release/extended-release (IR/ER) amantadine formulation OS320 (OSMOLEX ER®) contains an IR outer layer and ER core for once-daily dosing. Objective Report individual and pooled results for the similarly designed double-blind...

Amantadine is an old, antiviral compound, which moderately improves motor behavior in Parkinson's disease. Its current resurgence results from an innovative, delayed uptake and extended release amantadine hydrochloride capsule, given at bedtime once daily. It is the only approved compound for reduction of involuntary movements, so called dyskinesia...

Amantadin wurde aufgrund seiner antiviralen Eigenschaf-ten bereits in den frühen 60er-Jahren zur Vorbeugung und Behandlung der Influenza A auf den Markt gebracht. Die Anti-parkinson-Wirkung wurde erstmals 1969 beschrieben und in den folgenden Jahren durch mehrere Studien bestätigt. Neben den Kardinalsymptomen Rigor, Tremor und Brady-kinese kann Ama...

Previous trials describe a decrease of vitamin D levels in patients with Parkinson’s disease and relationships to clinical disease severity. This case control study found not significant but higher 25-OH-vitamin D plasma levels in patients with Parkinson’s disease patients compared with age and sex matched controls and no associations to clinical p...

Background: Vitamin D has a steroid- and an anabolic-resembling chemical structure. Vitamin D is essential for many processes in the human body after hydroxylation. Aims of the study: To investigate the impact of 25-hydroxy-vitamin D plasma concentrations on the blood parameters number of erythrocytes, hematocrit, mean corpuscular hemoglobin and...

The term idiopathic Parkinson's disease describes an entity of various not well-characterized disorders resembling each other. They are characterized by chronic neuronal dying originating from various disease mechanisms. They result in the onset of motor and related non-motor features, both of which respond to administration of personalized drug co...

Case presentation Repeated intrathecal application of the sustained release steroid Triamcinolone Acetonide (TCA) is beneficial in progressive Multiple Sclerosis (MS) patients [1]. Particularly, patients with spinal lesions often show a distinct benefit with a three fold increase of the maximum walking distance [2]. This therapy ameliorates walking...

A rare condition is temporary but recurrent onset of involuntary motion sequences in the abdominal region. They demands for an extensive diagnostic workup. Therapeutic options are limited. The successful treatment of this spinal myoclonus or abdominal involuntary movements resembling syndrome prompted this report.

Repeated intrathecal application of the sustained release steroid Triamcinolone Acetonide (TCA) is beneficial in progressive Multiple Sclerosis (MS) patients [1]. Particularly, patients with spinal lesions often show a distinct benefit with a three fold increase of the maximum walking distance [2]. This therapy ameliorates walking distance, improve...

Symptomatic treatments are available for Parkinson’s disease and Alzheimer’s disease. An unmet need is cure or disease modification. This review discusses possible reasons for negative clinical study outcomes on disease modification following promising positive findings from experimental research. It scrutinizes current research paradigms for disea...

Parkinson’s disease (PD) is the second most chronic neurodegenerative disorder worldwide. Deficit of monoamines, particularly dopamine, causes an individually varying compilation of motor and non-motor features. Constraint of presynaptic uptake extends monoamine stay in the synaptic cleft. This review discusses possible benefits of dopamine reuptak...

Objective: To characterize socio-demographic and disease-specific data of Parkinson's disease patients before and 1 year after therapy escalation with subcutaneous apomorphine (APO), levodopa/carbidopa intestinal gel (LCIG), or subthalamic deep brain stimulation (STN-DBS) in an observation trial under real life conditions. Methods: Between 2014-201...

The risk of failure was high when testing compounds in clinical programs for the treatment of dementia in the past. Probable fundamental reasons are the heterogeneity of symptom expression, use of inappropriate assessment instruments, safety and tolerability hurdles, too short study durations in Alzheimer disease modifying trials, intensive recruit...

Abstract Background The efficacy and safety of opicapone, a once-daily catechol-O-methyltransferase inhibitor, have been established in two large randomized, placebo-controlled, multinational pivotal trials. Still, clinical evidence from routine practice is needed to complement the data from the pivotal trials. Methods OPTIPARK (NCT02847442) was a...

Motor symptoms in patients with Parkinson’s disease may be determined with instrumental tests and rating procedures. Their outcomes reflect the functioning and the impairment of the individual patient when patients are tested off and on dopamine substituting drugs. Objectives were to investigate whether the execution speed of a handwriting task, in...

The long-term and potential rare side effects of new immunomodulating drugs for the treatment of multiple sclerosis (MS) are often not well known. Spontaneous case report systems of adverse drug effects are a valuable source in pharmacovigilance, but have several limitations. Primary data collections within registries allow a comprehensive analysis...

The deficiency pattern of neurotransmitters is heterogeneous in patients with Parkinson's disease. Consequence is an individual variable expression of motor and nonmotor features. They respond to agents with a broader spectrum of mode of actions, whereas dopamine substitution only targets impaired motor behavior. The pharmacological profile of safi...

Introduction Heterogeneity of symptoms and individual variability of progression characterizes Parkinson’s disease. Unmet therapeutic needs include a cure, disease modification, and improvement of available marketed dopamine-substituting compounds. Personalized treatment, tailored to the patients’ needs and symptoms, aims to ameliorate impaired mot...

Zusammenfassung COMT- und MAO-B-Hemmer gehören neben den Dopamin-Agonisten und Levodopa zu den etablierten Pharmaka zur Behandlung des idiopathischen Parkinson-Syndroms (IPS). Die MAO-B-Hemmer Selegilin und Rasagilin entfalten auch in der Monotherapie einen symptomatischen Therapieeffekt, während Safinamid und COMT-Hemmer nur zur Kombinationstherap...

Complementary therapies are an essential component of the treatment of patients with Parkinson's disease. They aim to ameliorate disease symptoms in conjunction with dopamine substitution. Kinesiology trains about the effective use of physical, mental and emotional skills. Objectives of this pilot study were to demonstrate the efficacy of a standar...

The majority of disease-modifying drugs (DMDs) available for the management of active relapsing–remitting multiple sclerosis (RMS) depend on continuous drug intake for maintained efficacy, with escalation to a more active drug when an unacceptable level of disease activity returns. Among continuously applied regimens, interferons and glatiramer ace...

Introduction: Parkinson’s disease is a chronic, neurodegenerative disease entity with heterogeneous features and course. Levodopa is the most efficacious dopamine substituting drug. Particularly, long term application of oral levodopa/decarboxylase inhibitor formulations sooner or later supports onset of fluctuations of movement. It also shifts lev...

ZUSAMMENFASSUNG Die Bildgebung mithilfe der Magnetresonanztomografie (MRT) hat eine immer größere Bedeutung für die Diagnose und das Monitoring der schubförmig-remittierenden Multiplen Sklerose (RRMS) erhalten. Entscheidend sind die Einhaltung von Qualitätsstandards bei der Durchführung der MRT und die Interpretation der MRT-Befunde im Zusammenhang...

Instrumental measurement of response assets and movement behaviour gained importance as addition to rating procedures to determine the efficacy of therapeutic interventions in patients with Parkinson’s disease. Objectives were to determine the response to standardised 100 mg levodopa application with repeat performance of complex and simple instrum...

Neurotransmission of biogenic monoamines such as dopamine is important for brain function. Biogenic amine degradation uses monoamine oxidase B in neuronal and glial cells. Inhibition monoamine oxidase B elevates biogenic amine concentration in the synaptic cleft. Thus monoamine oxidase B inhibitors provide a symptomatic effect on motor symptoms in...

The hyperechogenicity of the substania nigra (SN) has been established as a valid finding in patients with Parkinson´s disease (PD), probably caused by an increased tissue iron concentration in the SN. The application of transcranial sonography (TCS) has been investigated for further echogenic basal ganglia alterations in patients with extrapyramid...

The chemical structure of vitamin D resembles steroids and anabolics. Following activation by enzymatic hydroxylation, vitamin D enhances numerous body functions. We determined 25-hydroxy-vitamin D, number of erythrocytes, haematocrit, mean corpuscular haemoglobin and mean corpuscular volume in 97 patients with multiple sclerosis initially and 6 mo...

Peaks and troughs of levodopa in plasma contribute to pulsatile postsynaptic dopamine receptor stimulation in patients with Parkinson’s disease. Measurement of levodopa plasma levels mostly only considers the total levodopa plasma concentration. Objectives were to determine bound, free, and total plasma levodopa and to investigate their correlation...

Wie sehen aktuelle Zulassungsverfahren aus? Welche Rolle spielt die evidenzbasierte Medizin? Wie läuft die Finanzierung ab und werden Innovationen akzeptiert? Und wie passt das in unseren engen finanziellen Rahmen? Im Folgenden soll eine Diskussion über unser innovationsfeindliches System in Gang gebracht werden.

Onset of involuntary movement patterns of the face, body and limbs are known as dyskinesia. They mostly appear in association with long-term levodopa (l-dopa) therapy in patients with Parkinson’s disease. Consequences include patient distress, caregiver embarrassment and reduced quality of life. A severe intensity of this motor complication may res...

Parkinson’s disease (PD) comprises a spectrum of disorders with differing subtypes, the vast majority of which share Lewy bodies (LB) as a characteristic pathological hallmark. The process(es) underlying LB generation and its causal trigger molecules are not yet fully understood. α-Synuclein (α-syn) is a major component of LB and SNCA gene missense...

Parkinson's disease is associated with an increased risk of melanoma (and vice versa). Several hypotheses underline this link, such as pathways affecting both melanin and neuromelanin. For the first time, the fluorescence of melanin and neuromelanin is selectively accessible using a new method of nonlinear spectroscopy, based on a stepwise two-phot...

Introduction: Amantadine is an old, antiviral compound that moderately ameliorates impaired motor behaviour in Parkinson’s disease. Its current resurgence results from the novel retarded release amantadine hydrochloride formulation, ADS5102, which has also received approval for the treatment of levodopa-related involuntary movements known as dyskin...

Introduction: Brain function depends considerably on the neurotransmission of biogenic monoamines. Their metabolism employs monoamine oxidase-B in neuronal and glial cells. Inhibition of monoamine oxidase-B elevates biogenic amine levels. Accordingly, monoamine oxidase-B inhibitors provide a symptomatic effect via dopamine on motor symptoms in pati...

Objective To investigate whether increased fixed carbidopa doses of 65 or 105 mg (ODM-101/65 and ODM-101/105) in combination with 75, 100, 125, or 150 mg of levodopa and 200 mg of entacapone might improve “off” time in fluctuating Parkinson disease (PD) compared to the standard combination of 4:1 levodopa/carbidopa with the usual 200 mg of entacapo...

Introduction: Levodopa is the most efficacious and best-tolerated drug for treating Parkinson’s disease (PD). To improve the treatment of PD, recent research initiatives have aimed to optimize the pharmacokinetic plasma behavior of L-dopa. Areas covered: This non-systematic, narrative drug evaluation brings the therapeutic value of IPX066 up for di...

This invited narrative review emphasizes the role of MAO-B inhibition in the drug portfolio for dopamine substitution in patients with Parkinson’s disease. Neuronal and glial MAO-B inhibition contributes to more stable levels of dopamine and other biogenic amines in the synaptic cleft. Accordingly, symptomatic effects of MAO-B inhibition for a limi...

Background/Aims: Pain is a non-motor symptom of Parkinson’s disease (PD). Few systematic studies have been carried out and there are still no guidelines on pain therapy in PD. Additionally, within the studies that do exist, gender-specific differences in pain perception are often the focus, though no consistent results have to date been obtained. T...

T he Fourth Edition of the PD Academy, sponsored by Zambon, was held in Barcelona on 1-2 February 2018. During the pan-European event, world-renowned experts in Parkinson's disease (PD) presented the latest findings in the pathophysiology and management of the disease. Delegates attended a series of lectures by specialists that largely focused on n...

Zusammenfassung Daten aus epidemiologischen Studien, die mögliche Assoziationen bestimmter Nahrungsmittel mit dem Risiko an der Parkinson’schen Krankheit zu erkranken untersucht haben, suggerieren, dass manche Nahrungsmittel, wie z. B. nikotinreiche Paprika, dieses modifizieren können. Auch scheinen nach der Analyse einer Reihe von Medikamenten-Zul...

Zusammenfassung Hintergrund Wenig ist über die patientenseitig wahrgenommene Versorgungssituation des Morbus Parkinson in Deutschland bekannt. Im Einzelnen besteht ein gesteigertes Interesse der Versorgungsforschung, besser zu verstehen, welche Rolle verschiedene Akteure im Versorgungsprozess über den Krankheitsverlauf hinweg einnehmen, welche mögl...

Introduction: Parkinson’s disease is a chronic, neurodegenerative disease. Its symptoms and course are heterogeneous. After several years of investigative drug studies, levodopa remains the most efficacious drug despite its long-term limitations. Consequently, research into new drug delivery modes is ongoing. Areas covered: This review summarizes p...

Real-world data from large cohorts of patients with Parkinson’s disease on the long-term effectiveness of different dopamine-substituting drug therapies are rare. The objective of this study was to obtain information on real-world management of PD with dopamine-substituting drugs. SP0854 (NCT00599339) was a prospective, multicenter, non-interventio...

Heterogeneous expression of neurotransmitter deficits results from onset and progression of Parkinson’s disease. Intervals, characterized by reappearance of motor and associated certain nonmotor symptoms, determine the end of good tolerability and efficacy of oral levodopa therapy. These “OFF” states result from levodopa pharmacokinetics and diseas...

Visual dysfunction is common in patients with Parkinson’s disease (PD). The objective of this study was to investigate the perceived impact of visual dysfunction and especially color vision loss on PD patients, and to identify retinal and disease factors associated with color vision. Thirty PD patients and thirty-four healthy controls were included...

Introduction: The ABCB1 (P-gp, MDR1, CD243) transporters system plays an eminent role in brain detoxification. It protects against endogenous and exogenous toxin transport into the brain parenchyma by supporting toxin efflux over the blood brain barrier. Areas covered: This editorial discusses the role and pro’s and con’s of ABCB1 modulation in the...

In ruhigen Momenten zittert der Körper, die Skelettmuskulatur erstarrt zunehmend, dazu ein Maskengesicht, verlangsamte Bewegungen und eine leise Stimme: Dies alles können Symptome eines Parkinson-Syndroms sein. Die Vielfalt der Symptome macht die Krankheit so komplex und erfordert fachkundige Pflegemaßnahmen.

Introduction Chronic intake of typical neuroleptics or centrally acting dopamine receptor blocking antiemetics may cause onset of tardive syndromes. Various types exist. One of them is tardive dyskinesia, characterised by often stigmatising, purposeless, rapid, repetitive, stereotypic, involuntary movements of face, limbs or trunk. Effective sympto...

Introduction: Parkinson's disease is characterized by a heterogeneous combination of motor and non motor symptoms. The nigrostriatal dopamine deficit is one of its essential pathophysiologic features. Areas covered: This invited narrative review provides an overlook over current available and future promising non dopaminergic therapeutics to modul...

Background: Mood disorders are very frequent in Parkinson's Disease (PD), and their effective treatment is still a major unresolved issue: growing evidence suggests that glutamatergic system dysfunction is directly involved. Safinamide is a drug with an innovative mechanism of action, dopaminergic and non-dopaminergic, that includes the reversible...

Advanced stages of Parkinson’s disease (advPD) still impose a challenge in terms of classification and related stage-adapted treatment recommendations. Previous concepts that define advPD by certain milestones of motor disability apparently fall short in addressing the increasingly recognized complexity of motor and non-motor symptoms and do not al...

Background: Biogenic amines and monoamine oxidase inhibitors influence peripheral monoamine oxidase enzyme activity in chronic levodopa/dopa decarboxylase inhibitor-treated patients with Parkinson disease. Rasagiline is an irreversible inhibitor of monoamine oxidase B. Safinamide blocks this isoenzyme in a reversible fashion. Objectives: The aim...

Introduction: Patients with Parkinson’s disease suffer from a heterogeneous expression of neurotransmitter deficits. They cause an individual variable expression of motor and non-motor symptoms. Thus, drugs with various mechanisms of actions are suitable to counteract these disease related neurotransmitter alterations. Areas covered: This invited r...