Martin M Reich

University Hospital Würzburg · Department of Neurology

Background Dystonia is a neurological movement disorder characterised by abnormal involuntary movements and postures, particularly affecting the head and neck. However, current clinical assessment methods for dystonia rely on simplified rating scales which lack the ability to capture the intricate spatiotemporal features of dystonic phenomena, hind...

Background: Deep brain stimulation of the internal globus pallidus effectively alleviates dystonia motor symptoms. However, delayed symptom control and a lack of therapeutic biomarkers and a single pallidal sweetspot region complicates optimal programming. Postoperative management is complex, typically requiring multiple, lengthy follow-ups with a...

b> Introduction: Computational models of deep brain stimulation (DBS) have become common tools in clinical research studies that attempt to establish correlations between stimulation locations in the brain and behavioral outcome measures. However, the accuracy of any patient-specific DBS model depends heavily upon accurate localization of the DBS e...

Projekthintergründe Mit der tiefen Hirnstimulation steht für die neurologische Erkrankungen der Bewegungsstörung eine hocheffektive Behandlungsmethode zur Verfügung, welche aufgrund seiner Effektivität bei schwerem Tremor und Dystonien sowie bei der fortgeschrittenen Parkinson-Erkrankung einen zunehmend hohen klinischen Stellenwert genießt. Verbess...

Research on the mental rotation task has sparked debate regarding the specific processes that underly the capability of humans to mentally rotate objects. The spread of reported brain activations suggests that mental rotation is subserved by a neural network circle. However, no common network has yet been found that uncovers the crucial processes u...

The frontal cortex is involved in motor, cognitive, and affective brain functions. In humans, however, neuroanatomy-function mappings are predominantly derived from correlative neuroimaging studies. Hence, exactly which frontal domains causally mediate which function remains largely elusive. Herein, we leverage a strategy that allows for causal inf...

Background: Deep brain stimulation of the subthalamic nucleus is an effective treatment of Parkinson's disease, yet it is often associated with a general deterioration of speech intelligibility. Clustering the phenotypes of dysarthria has been proposed as a strategy to tackle these stimulation-induced speech problems. Methods: In this study, we...

Objective Gait disturbances causing impaired mobility are common in Parkinson’s disease after bilateral deep brain stimulation of the subthalamic nucleus. We describe subthalamic subregions where neurostimulation had a positive effect on gait or provoked gait disturbances. Methods Sixty-eight patients were classified according to postoperative gai...

Background Subthalamic nucleus (STN) deep brain stimulation (DBS) is regarded as an effective treatment for patients with advanced Parkinson’s disease (PD). Clinical benefit, however, varies significantly across patients. Lead location has been hypothesized to play a critical role in determining motor outcome and may account for much of the observe...

Introduction: Over the past decades, research on the mental rotation task has sparked debate regarding the specific processes that underly the unique capability of humans to mentally rotate objects. The spread of reported brain activations, including visual, motor and cognitive nodes such as premotor and supplementary motor area (SMA), inferior and...

Background: Deep brain stimulation (DBS) is an established therapy for patients with Parkinson’s disease. In silico computer models for DBS hold the potential to inform a selection of stimulation parameters. In recent years, the focus has shifted towards DBS-induced firing in myelinated axons, deemed particularly relevant for the external modulatio...

Introduction: Deep Brain Stimulation (DBS) of the (sub)thalamic nucleus has been shown to be an effective treatment in medication-refractory Essential Tremor (ET). However, studies have reported a DBS-induced ataxia in some patients which can onset years after the start of DBS-therapy. In the ongoing debate on the cause a functional disruption of t...

Background: Phenomenological description, diagnosis and assessment of disease development, as well as treatment effects, of movement disorders still heavily relies on clinical assessment using scoring scales. However, these scales are inherently prone to rater biases, thereby negatively affecting their reliability and comparability. Objective: To l...

Introduction: Tremor is defined as an involuntary, rhythmic oscillatory movement of a body part and represents one of the most common symptoms in movement disorders, existing across several diseases. Particularly, in advanced states of tremor-related diseases such as Parkinson’s disease (PD) and Essential tremor syndrome (ET), response to pharmacot...

Introduction: Nucleus Basalis of Meynert (NBM) is a cholinergic relay in the basal forebrain that has a role in cognition. Postmortem studies reveal projections to cortical and subcortical cognitive-related areas. In cases of Alzheimer’s and Parkinson’s disease dementia (PDD) patients, it suffers cellular degeneration[1]. Deep Brain Stimulation (DB...

Introduction: Clinimetrics of movement disorders relies on scales such as the Fahn-Tolosa-Marin Tremor Rating Scale for Essential Tremor (ET). However, these rating scales are prone to rater bias. Quantitative measurements of tremor kinematics, which are proxy measures of clinical outcome, can be achieved with gold standard tremor analyses using re...

Background: The thalamic ventral intermediate (Vim) nucleus is part of a network that appears to be disrupted in essential tremor (ET) and is the most relevant target of functional neurosurgery to alleviate ET symptoms. As the most important afferent of the VIM, the cerebellothalamic tract (CTT) transmits information from cerebellar nuclei. Disrupt...

Deep brain stimulation (DBS) of the subthalamic nucleus or the globus pallidus is an established treatment for Parkinson’s disease (PD) that yields a marked and lasting improvement of motor symptoms. Yet, DBS benefit on gait disturbances in PD is still debated and can be a source of dissatisfaction and poor quality of life. Gait disturbances in PD...

Dystonia is a debilitating disease with few treatment options. One effective option is deep brain stimulation (DBS) to the internal pallidum. While cervical and generalized forms of isolated dystonia have been targeted with a common approach to the posterior third of the nucleus, large-scale investigations regarding optimal stimulation sites and po...

Objective: Deep brain stimulation (DBS) of the thalamic ventral intermediate nucleus (VIM) effectively suppresses arm tremor. Uncontrolled studies suggest the posterior subthalamic area (PSA) may be superior. We compared the intra-individual efficacy of VIM- versus PSA-DBS on tremor suppression and arm function. Methods: We performed a randomize...

Background and purpose: The aim was to characterize a combined vestibular, ocular motor and postural syndrome induced by deep brain stimulation (DBS) of the subthalamic nucleus in a patient with Parkinson's disease. Methods: In a systematic DBS programming session, eye, head and trunk position in roll and pitch plane were documented as a functio...

Deep brain stimulation (DBS) is an effective treatment for Parkinson’s disease but can be complicated by side-effects such as cognitive decline. There is often a delay before this side-effect is apparent and the mechanism is unknown, making it difficult to identify patients at risk or select appropriate DBS settings. Here, we test whether connectiv...

Deep brain stimulation is an effective treatment for Parkinson’s disease but can be complicated by side-effects such as cognitive decline. There is often a delay before this side-effect is apparent and the mechanism is unknown, making it difficult to identify patients at risk or select appropriate deep brain stimulation settings. Here, we test whet...

Introduction Deep brain stimulation of the internal globus pallidus is an effective treatment for dystonia. However, there is a large variability in clinical outcome with up to 25% non-responders even in highly selected primary dystonia patients. In a large cohort of patients we recently demonstrated that the variable clinical outcomes of pallidal...

Objectives: Deep brain stimulation (DBS) programming is based on clinical response testing. Our clinical pilot trial assessed the feasibility of image-guided programing using software depicting the lead location in a patient-specific anatomical model. Methods: Parkinson's disease patients with subthalamic nucleus-DBS were randomly assigned to stand...

Deep brain stimulation (DBS) is an established therapy for patients with Parkinson’s disease. In silico computer models for DBS allow to pre-select a set of potentially optimal stimulation parameters. If efficacious, they could further carry insight into the mechanism of action of DBS and foster the development of more efficient stimulation approac...

Background: Probabilistic brain mapping is a promising tool to estimate the expected benefit of pallidal deep brain stimulation (GPi-DBS) in patients with isolated dystonia (IsoD). Objectives: To investigate the role of probabilistic mapping in combined dystonia (ComD). Methods: We rendered the pallidal atlas and the volume of tissue activated...

The subthalamic nucleus and internal pallidum are main target sites for deep brain stimulation in Parkinson’s disease. Multiple trials that investigated subthalamic versus pallidal stimulation were unable to settle on a definitive optimal target between the two. One reason could be that the effect is mediated via a common functional network. To tes...

Deep brain stimulation (DBS) of the thalamic ventral intermediate nucleus is one of the main advanced neurosurgical treatments for drug-resistant tremor. However, not every patient may be eligible for this procedure. Nowadays, various other functional neurosurgical procedures are available. In particular cases, radiofrequency thalamotomy, focused u...

Dystonia is a debilitating disease with few conservative treatment options but many types of isolated dystonia can be effectively treated using deep brain stimulation (DBS) to the internal pallidum. While cervical and generalized forms of isolated dystonia have been targeted with a common approach to the posterior third of the nucleus, large-scale...

Objective: To report a patient with Parkinson’s disease presenting with a combined vestibular, oculomotor and postural syndrome dependent of deep brain stimulation (DBS) of the subthalamic nucleus. Methods: In a systematic monopolar review, eye, head and trunk position in roll and pitch plane were documented as a function of stimulation amplitude a...

The subthalamic nucleus and internal pallidum are main target sites for deep brain stimulation in Parkinson's disease. Multiple trials that investigated subthalamic versus pallidal stimulation were unable to settle on a definitive optimal target between the two. One reason could be that the effect is mediated via a common network. To test this hypo...

Background: Deep brain stimulation of the globus pallidus interna (GPi-DBS) is a highly efficacious treatment for cervical dystonia. Typically, the treatment response is delayed, appearing and increasing even months after implantation. However, it is not known how fast the symptoms reappear and whether there is a long-term therapeutic effect after...

Background: Deep brain stimulation (DBS) is an effective evidence-based therapy for dystonia. However, no unequivocal predictors of therapy responses exist. We investigate whether patients optimally responding to DBS present distinct brain network organization and structural patterns. Methods: Eighty-two dystonia patients with segmental and general...

Freezing of gait is a disabling symptom of Parkinson’s disease that causes a paroxysmal inability to generate effective stepping. The underlying pathophysiology has recently migrated towards a dysfunctional supraspinal locomotor network, but the actual network derangements during ongoing gait freezing are unknown. We investigated the communication...

Introduction: Striatal dopamine depletion disrupts basal ganglia function and causes Parkinson’s disease (PD). The pathophysiology of the dopamine-dependent relationship between basal ganglia signaling and motor control, however, is not fully understood. We obtained simultaneous recordings of local field potentials (LFPs) from the subthalamic nucle...

Deep brain stimulation of the internal globus pallidus is a highly effective and established therapy for primary generalized and cervical dystonia, but therapeutic success is compromised by a non-responder rate of up to 25%, even in carefully-selected groups. Variability in electrode placement and inappropriate stimulation settings may account for...

Cervical dystonia is a neurological disorder characterized by sustained, involuntary movements of the head and neck. Most cases of cervical dystonia are idiopathic, with no obvious cause, yet some cases are acquired, secondary to focal brain lesions. These latter cases are valuable as they establish a causal link between neuroanatomy and resultant...

Background: Clinical trials have established subthalamic deep-brain-stimulation (STN-DBS) as a highly effective treatment for motor symptoms of Parkinson disease (PD), but in clinical practice outcomes are variable. Experienced centers are confronted with an increasing number of patients with partially "failed" STN-DBS, in whom motor benefit doesn...

Background: Cervical dystonia is a movement disorder causing abnormal postures and movements of the head. While the exact pathophysiology of cervical dystonia has not yet been fully elucidated, a growing body of evidence points to the cerebellum as an important node. Methods: Here, we examined the impact of cerebellar interference by transcranial m...

Background: Deep brain stimulation (DBS) is an effective evidence-based therapy for dystonia. However, no unequivocal predictors of therapy responses exist. We investigate whether patients optimally responding to DBS present distinct brain network organization and structural patterns. Methods: Based on a German multicentre cohort of eighty-two dyst...

Brain damage can occasionally result in paradoxical functional benefit, which could help identify therapeutic targets for neuromodulation. However, these beneficial lesions are rare and lesions in multiple different brain locations can improve the same symptom. Using a technique called lesion network mapping, we show that heterogeneous lesion locat...

Background: The onset of multiple system atrophy (MSA) before age 40 years is referred to as "young-onset MSA." We identified clinical and pathological characteristics that might help with its early diagnosis and distinction from young-onset Parkinson's disease and late-onset MSA. Methods: We reviewed the available clinical and pathological feat...

Background STB DBS (deep brain stimulation of the subthalamic nucleus) is commonly used to treat advanced Parkinson disease (PD) while posterior hypothalamic DBS for cluster headache (CH) remains experimental. Methods We present a case where a middle-aged man was diagnosed with both CH and PD and received medical treatment for both. The patient wa...

Background: Stimulation parameters in deep brain stimulation (DBS) of the subthalamic nucleus for Parkinson's disease (PD) are rarely tested in double-blind conditions. Evidence-based recommendations on optimal stimulator settings are needed. Results from the CUSTOM-DBS study are reported, comparing 2 pulse durations. Methods: A total of 15 pati...

Objective: The benefit of deep brain stimulation (DBS) for Parkinson's disease (PD) may depend on connectivity between the stimulation site and other brain regions, but which regions and whether connectivity can predict outcome in patients remains unknown. Here, we identify the structural and functional connectivity profile of effective DBS to the...

BACKGROUND The benefit of deep brain stimulation (DBS) for Parkinson’s disease (PD) may depend on connectivity between the stimulation site and other brain regions, but which regions and whether connectivity can predict outcome in patients remains unknown. Here, we identify the structural and functional connectivity profile of effective DBS to the...

Background: The threshold current for inducing muscle contractions by stimulation of pyramidal tract fibres adjacent to the globus pallidus internus (GPi) is, besides microelectrode recordings for the determination of nuclear boundaries, currently the only neurophysiological marker for intraoperative refinement of the anatomically planned target p...

Activation of the basal ganglia has been shown during the preparation and execution of movement. However, the functional interaction of cortical and subcortical brain areas during movement and the relative contribution of dopaminergic striatal innervation remain unclear. We recorded local field potential activity from the subthalamic nucleus and hi...

View largeDownload slide Deep brain stimulation for essential tremor is complicated in some patients by the progressive evolution of severe gait ataxia. Using a combined clinical and neuroimaging approach, Reich et al . provide evidence that the ataxia is a stimulation-related adverse effect, and propose a pathophysiological model to explain its o...

Background In previous work (Carcieri et al.), we observed impedance changes during the measurement of efficacy and side effect thresholds in seven DBS patients. This study investigates a larger group of subjects with more frequent impedance measurements to better characterize the time course of the effect and tests whether electrode impedance vari...

Introduction: Deep brain stimulation (DBS) is effective for some neurological and psychiatric conditions. Idiopathic delayed-onset edema (IDE) surrounding the leads has been anecdotally reported. The etiology, predisposing factors and prognosis of this complication are unknown. We present a multicenter case series of patients with IDE, and a syste...

We explored the impact of pulse durations <60 μsec on the therapeutic window of subthalamic neurostimulation in Parkinson's disease. Current thresholds for full rigidity control and first muscle contractions were evaluated at pulse durations between 20 and 120 μsec during a monopolar review session in four patients. The average therapeutic window w...

GTP cyclohydrolase 1, encoded by the GCH1 gene, is an essential enzyme for dopamine production in nigrostriatal cells. Loss-of-function mutations in GCH1 result in severe reduction of dopamine synthesis in nigrostriatal cells and are the most common cause of DOPA-responsive dystonia, a rare disease that classically presents in childhood with genera...

GTP cyclohydrolase 1, encoded by the GCH1 gene, is an essential enzyme for dopamine production in nigrostriatal cells. Loss-of-function mutations in GCH1 result in severe reduction of dopamine synthesis in nigrostriatal cells and are the most common cause of DOPA-responsive dystonia, a rare disease that classically presents in childhood with genera...