Ritesh A. Ramdhani

What's special about task in dystonia? A voxel‐based morphometry and diffusion weighted imaging study

Numerous brain imaging studies have demonstrated structural changes in the basal ganglia, thalamus, sensorimotor cortex, and cerebellum across different forms of primary dystonia. However, our understanding of brain abnormalities contributing to the clinically well‐described phenomenon of task specificity in dystonia remained limited. We used high‐resolution magnetic resonance imaging (MRI) with voxel‐based morphometry and diffusion weighted imaging with tract‐based spatial statistics of fractional anisotropy to examine gray and white matter organization in two task‐specific dystonia forms, writers cramp and laryngeal dystonia, and two non–task‐specific dystonia forms, cervical dystonia and blepharospasm. A direct comparison between both dystonia forms indicated that characteristic gray matter volumetric changes in task‐specific dystonia involve the brain regions responsible for sensorimotor control during writing and speaking, such as primary somatosensory cortex, middle frontal gyrus, superior/inferior temporal gyrus, middle/posterior cingulate cortex, and occipital cortex as well as the striatum and cerebellum (lobules VI‐VIIa). These gray matter changes were accompanied by white matter abnormalities in the premotor cortex, middle/inferior frontal gyrus, genu of the corpus callosum, anterior limb/genu of the internal capsule, and putamen. Conversely, gray matter volumetric changes in the non–task‐specific group were limited to the left cerebellum (lobule VIIa) only, whereas white matter alterations were found to underlie the primary sensorimotor cortex, inferior parietal lobule, and middle cingulate gyrus. Distinct microstructural patterns in task‐specific and non–task‐specific dystonias may represent neuroimaging markers and provide evidence that these two dystonia subclasses likely follow divergent pathophysiological mechanisms precipitated by different triggers.

Primary Dystonia: Conceptualizing the Disorder through a Structural Brain Imaging Lens

Background Dystonia is a hyperkinetic movement disorder characterized by involuntary, repetitive twisting movements. The anatomical structures and pathways implicated in its pathogenesis and their relationships to the neurophysiological paradigms of abnormal surround inhibition, maladaptive plasticity, and impaired sensorimotor integration remain unclear. Objective We review the use of high-resolution structural brain imaging using voxel-based morphometry (VBM) and diffusion tensor imaging (DTI) techniques for evaluating brain changes in primary torsion dystonia and their relationships to the pathophysiology of this disorder. Methods A PubMed search was conducted to identify relevant literature. Results VBM and DTI studies produced somewhat conflicting results across different forms of primary dystonia and reported increases, decreases, or both in gray matter volume and white matter integrity. However, despite the discrepancies, these studies are consistent in revealing brain abnormalities in dystonia that extend beyond the basal ganglia and involve the sensorimotor cortex and cerebellum. Discussion Although limited to date, structural magnetic resonance imaging (MRI) studies combined with functional brain imaging and neurophysiological modalities begin to establish structural-functional relationships at different levels of the abnormal basal ganglia, cortical, and cerebellar networks and provide clues into the pathophysiological mechanisms that underlie primary dystonia. Cross-disciplinary studies are needed for further investigations of the interplay between structural-functional brain abnormalities and environmental and genetic risk factors in dystonia patients.

Early Use of 60 Hz Frequency Subthalamic Stimulation in Parkinson's Disease: A Case Series and Review.

Deep brain stimulation (DBS) is effective in treating the segmental symptoms of Parkinsons disease (PD) as well as axial symptoms that are levodopa responsive. PD patients on chronic DBS who develop axial symptoms and gait disturbances several years later oftentimes are refractory to high frequency stimulation (HFS). Several studies report benefit produced by low frequency subthalamic nucleus (STN) stimulation in such patients, though the sustainability of the effects has been mixed.

Isolated Focal Dystonia as a Disorder of Large-Scale Functional Networks

Abstract Isolated focal dystonias are a group of disorders with diverse symptomatology but unknown pathophysiology. Although recent neuroimaging studies demonstrated regional changes in brain connectivity, it remains unclear whether focal dystonia may be considered a disorder of abnormal networks. We examined topology as well as the global and local features of large‐scale functional brain networks across different forms of isolated focal dystonia, including patients with task‐specific (TSD) and nontask‐specific (NTSD) dystonias. Compared with healthy participants, all patients showed altered network architecture characterized by abnormal expansion or shrinkage of neural communities, such as breakdown of basal ganglia‐cerebellar community, loss of a pivotal region of information transfer (hub) in the premotor cortex, and pronounced connectivity reduction within the sensorimotor and frontoparietal regions. TSD were further characterized by significant connectivity changes in the primary sensorimotor and inferior parietal cortices and abnormal hub formation in insula and superior temporal cortex, whereas NTSD exhibited abnormal strength and number of regional connections. We suggest that isolated focal dystonias likely represent a disorder of large‐scale functional networks, where abnormal regional interactions contribute to network‐wide functional alterations and may underline the pathophysiology of isolated focal dystonia. Distinct symptomatology in TSD and NTSD may be linked to disorder‐specific network aberrations.

Neural correlates of abnormal sensory discrimination in laryngeal dystonia

Aberrant sensory processing plays a fundamental role in the pathophysiology of dystonia; however, its underpinning neural mechanisms in relation to dystonia phenotype and genotype remain unclear. We examined temporal and spatial discrimination thresholds in patients with isolated laryngeal form of dystonia (LD), who exhibited different clinical phenotypes (adductor vs. abductor forms) and potentially different genotypes (sporadic vs. familial forms). We correlated our behavioral findings with the brain gray matter volume and functional activity during resting and symptomatic speech production. We found that temporal but not spatial discrimination was significantly altered across all forms of LD, with higher frequency of abnormalities seen in familial than sporadic patients. Common neural correlates of abnormal temporal discrimination across all forms were found with structural and functional changes in the middle frontal and primary somatosensory cortices. In addition, patients with familial LD had greater cerebellar involvement in processing of altered temporal discrimination, whereas sporadic LD patients had greater recruitment of the putamen and sensorimotor cortex. Based on the clinical phenotype, adductor form-specific correlations between abnormal discrimination and brain changes were found in the frontal cortex, whereas abductor form-specific correlations were observed in the cerebellum and putamen. Our behavioral and neuroimaging findings outline the relationship of abnormal sensory discrimination with the phenotype and genotype of isolated LD, suggesting the presence of potentially divergent pathophysiological pathways underlying different manifestations of this disorder.

Isolated Chorea Associated with LGI1 Antibody

Background Leucine-rich glioma inactivated 1 (LGI1) antibody produces a syndrome of limbic encephalitis, hyponatremia, and facio-brachial dystonic seizures that is non-paraneoplastic and responsive to corticosteroids. Parkinsonism, tremor, and generalized chorea are rare manifestations of LGI1, but, when present, commonly accompany other signs of limbic encephalitis. Case Report We present a case of LGI1-related isolated chorea in a 53-year-old Japanese male. His chorea responded to high-dose steroids, suggesting a potential role for this synaptic antibody in triggering chorea. Discussion This case highlights a new treatable etiology of chorea.

Adult-onset Idiopathic Focal Lower Extremity Dystonia: A Rare Task-Specific Dystonia

Background Adult-onset focal lower extremity (LE) dystonia is rare, but there have recently been a number of case series that have reported an idiopathic variant triggered during ambulation. Methods We describe nine patients with idiopathic, focal task-specific LE dystonia. We conducted a comparative analysis that included our cohort and several recently published case series to further characterize the disorder. Results A total of 48 patients (37 female, 11 male) were compared. The average age of onset was 48 years; 36 patients had distal extremity involvement (75%), 5 proximal (10%), and 7 both proximal and distal (15%). Among 33 patients in which the dystonic side was known, 20 were affected on the left (61%). Inversion of the foot with flexion of one or more toes was the most prevalent pattern in those with distal extremity involvement. Discussion This is a novel task-specific dystonia triggered during ambulation that is often misdiagnosed as an orthopedic or psychogenic issue.

Pseudobulbar laughter as a levodopa off phenomenon exacerbated by subthalamic deep brain stimulation

Pseudobulbar affect is a common symptom in neurodegenerative diseases and can also result from lesions in cortical, subcortical and brainstem regions. In Parkinson’s disease (PD), pseudobulbar affect (PBA) can occur as a wearing off phenomenon, manifested usually as crying without emotionality. In addition, subthalamic (STN) deep brain stimulation (DBS) has been reported to induce PBA in PD patients with no prior history of such episodes.We present a case of inappropriate laughter lacking mirth as a levodopa OFF phenomenon in a patient with PD, whose laughter also worsened with STN-DBS in his non-medicated state. Levodopa ameliorated his PBA both with and without stimulation.The case demonstrates pseudobulbar laughter as a levodopa OFF phenomenon that is also exacerbated by STN-DBS.

Improvement of Post-hypoxic Myoclonus with Bilateral Pallidal Deep Brain Stimulation: A Case Report and Review of the Literature

Background Post-hypoxic myoclonus (PHM) is a syndrome that occurs when a patient has suffered hypoxic brain injury. The myoclonus is usually multifocal and generalized, often stemming from both cortical and subcortical origins. In severe cases, pharmacological treatments with antiepileptic medications may not satisfactorily control the myoclonus. Methods We present a case of a 23-year-old male with chronic medication refractory PHM following a cardiopulmonary arrest related to an asthmatic attack who improved with bilateral globus pallidus internus (GPi) deep brain stimulation (DBS). We review the clinical features of PHM, as well as the preoperative and postoperative Unified Myoclonus Rating Scale scores and DBS programming parameters in this patient and compare them with the three other published PHM-DBS cases in the literature. Results This patient experienced an alleviation of myoclonic jerks at rest and a 39% reduction in action myoclonus with improvement in both positive and negative myoclonus with bilateral GPi-DBS. High frequency stimulation (130 Hz) with amplitudes >2.5 V were needed for the therapeutic response. Discussion We demonstrate a robust improvement in a medication refractory PHM patient with bilateral GPi-DBS, and suggest that it is a viable therapeutic option for debilitating post-hypoxic myoclonus.

Stratifying Parkinson's Patients With STN‐DBS Into High‐Frequency or 60 Hz‐Frequency Modulation Using a Computational Model

High frequency stimulation (HFS) of the subthalamic nucleus (STN) is a well‐established therapy for Parkinsons disease (PD), particularly the cardinal motor symptoms and levodopa induced motor complications. Recent studies have suggested the possible role of 60 Hz stimulation in STN‐deep brain stimulation (DBS) for patients with gait disorder. The objective of this study was to develop a computational model, which stratifies patients a priori based on symptomatology into different frequency settings (i.e., high frequency or 60 Hz).