Papers by Raymond L Rosales
Journal of the Neurological Sciences, Oct 1, 2017
International Journal of Neuroscience, Nov 3, 2010
European neurological review, 2016
NeuroImage: Clinical, 2018
Preliminary evidence from postmortem studies of X-linked dystonia-parkinsonism (XDP) suggests tis... more Preliminary evidence from postmortem studies of X-linked dystonia-parkinsonism (XDP) suggests tissue loss may occur first and/or most severely in the striatal striosome compartment, followed later by cell loss in the matrix compartment. However, little is known about how this relates to pathogenesis and pathophysiology. While MRI cannot visualize these striatal compartments directly in humans, differences in relative gradients of afferent cortical connectivity across compartments (weighted toward paralimbic versus sensorimotor cortex, respectively) can be used to infer potential selective loss in vivo. In the current study we evaluated relative connectivity of paralimbic versus sensorimotor cortex with the caudate and putamen in 17 individuals with XDP and 17 matched controls. Although caudate and putamen volumes were reduced in XDP, there were no significant reductions in either "matrix-weighted", or "striosome-weighted" connectivity. In fact, paralimbic connectivity with the putamen was elevated, rather than reduced, in XDP. This was driven most strongly by elevated putamen connectivity with the anterior insula. There was no relationship of these findings to disease duration or striatal volume, suggesting insula and/or paralimbic connectivity in XDP may develop abnormally and/or increase in the years before symptom onset.
European Journal of Neurology, Feb 25, 2017
Background and purpose: X-linked dystonia-parkinsonism (XDP) is an inherited neurodegenerative ad... more Background and purpose: X-linked dystonia-parkinsonism (XDP) is an inherited neurodegenerative adult-onset movement disorder associated with striatal atrophy. As the dopaminergic system has not yet been systemically studied in this basal ganglia model disease, it is unclear whether nigrostriatal dysfunction contributes to parkinsonism in XDP. Methods: Pre-and post-synaptic dopaminergic function was assessed in XDP. A total of 10 123 jod-benzamide (IBZM) single-photon emission computed tomography (SPECT) images were obtained for nine patients aged 42.3 AE 9.5 years (SD; range 30-52) and one asymptomatic mutation carrier (38 years), and four ioflupane (FP-CIT) SPECT images were obtained for four patients, aged 41.5 AE 11.6 years (range 30-52 years). Structural magnetic resonance imaging was also performed for all mutation carriers and 10 matched healthy controls. Results: All patients were men who suffered from severe, disabling segmental or generalized dystonia and had varying degrees of parkinsonism. IBZM SPECT images were pathological in 8/9 symptomatic patients with distinct reduced post-synaptic tracer uptake in the caudate nucleus and putamen, and unremarkable in the asymptomatic mutation carrier. Longer disease duration was correlated with lower IBZM binding ratios. All subjects exhibited slightly reduced FP-CIT uptake values compared to controls for each analyzed region (À37% to À41%) which may be linked to basal ganglia volume loss. Visual inspection revealed physiological FP-CIT uptake in 1/4 patients. Conclusions: This nuclear imaging study provides evidence that the functional decline of post-synaptic dopaminergic neurotransmission is related to disease duration and ongoing neurodegeneration. Given the severe striatal cell loss which could be verified with post-synaptic nuclear imaging, both parkinsonism and dystonia in XDP are probably mainly due to striatal dysfunction.
Journal of Movement Disorders, Oct 30, 2010
Dr. Rosales does consulting agreements and speaking engagements for Ipsen Pharmaceuticals. He has... more Dr. Rosales does consulting agreements and speaking engagements for Ipsen Pharmaceuticals. He has performed clinical researches sponsored by Ipsen and Allergan through a contract with the University of Santo Tomas and the CNS of Metropolitan Medical Center in Manila. As president of the Movement Disorders Society of the Philippines, he has worked with and developed collaborative projects with the XDP study group, which are intended for the XDP cause. The author alone is responsible for the content and writing of the manuscript.
Movement Disorders, Jan 6, 2017
Background: Executive functions including behavioral adaptation and impulse control are commonly ... more Background: Executive functions including behavioral adaptation and impulse control are commonly impaired in movement disorders caused by striatal pathology. However, as yet it is unclear what aspects of behavioral abnormalities are related to pathology in which striatal subcomponent, that is, the matrix and the striosomes. We therefore studied cognitive control in X-linked dystonia-parkinsonism, a model disease of striosomal degeneration, using behavioral paradigms and EEG. Methods: We studied genetically confirmed X-linked dystonia-parkinsonism patients (N 5 21) in their early disease stages and healthy matched controls. Error-related behavioral adaptation was tested in a flanker task and response inhibition in a Go/Nogo paradigm during EEG. We focused on error-related negativity during error processing and the Nogo-N2 and Nogo-P3 in the response inhibition task. Source localization analyses were calculated. In addition, total wavelet power and phase-locking factor reflecting neural synchronization processes in time and frequency across trials were calculated. Results: Error processing and behavioral adaptation predominantly engaging the anterior cingulate cortex was markedly impaired in X-linked dystonia-parkinsonism. This was reflected in abnormal reaction times correlating with error-related negativity amplitudes, error related theta band activity, and the phase-locking factor. Also, abnormal error processing correlated with dystonia severity but not with parkinsonism. Response inhibition and corresponding EEG activity were normal. Conclusions: This dissociable pattern of cognitive deficits most likely reflects predominant dysfunction of the striosomal compartment and its connections to the anterior cingulate cortex in X-linked dystonia-parkinsonism. The results underscore the importance of striosomes for cognitive function in humans and suggest that striosomes are relays of error-related behavioral adaptation but not inhibitory control. V
Brain, Aug 28, 2018
X-linked dystonia-parkinsonism is a neurodegenerative movement disorder characterized by adult-on... more X-linked dystonia-parkinsonism is a neurodegenerative movement disorder characterized by adult-onset dystonia combined with parkinsonism over the disease course. Previous imaging and pathological findings indicate exclusive striatal atrophy with predominant pathology of the striosomal compartment in the dystonic phase of X-linked dystonia-parkinsonism. The striosome occupies 10-15% of the entire striatal volume and the density of striosomes follows a rostrocaudal gradient with the rostral striatum being considered striosome-rich. Recent quantitative MRI analyses provided evidence for an additional involvement of the white matter and the pallidum. In this study, we aimed to (i) disentangle the degree of atrophy in the different subdivisions of the striatum; (ii) investigate changes of cortical morphology; and (iii) elucidate the role of the cerebellum in X-linked dystonia-parkinsonism. T1-weighted MRI scans were acquired in 17 male X-linked dystonia-parkinsonism patients with predominant dystonia (40.1 ± 7.5 years) and 17 ethnicity-matched male healthy controls (35.2 ± 7.4 years). Voxel-based morphometry used a region of interest-based approach for the basal ganglia and primary motor cortex, whole brain analysis, and a separate analysis of the cerebellum. Cortical thickness and subcortical volume were measured. Volume loss in X-linked dystonia-parkinsonism affected all parts of the striatum (-29% voxel intensity) but was most pronounced in the associative subdivision (-41%; P < 0.001). The volume loss also involved the external and internal pallidum, albeit to a lesser extent than the striatum (-19% and -12%, P<0.001). Cortical thickness was reduced in the frontal (-4.3%) and temporal cortex (-6.1%). In addition, we found grey matter pathology in the associative part of the cerebellum and increased voxel intensities in the anterior sensorimotor part of the cerebellum and the dorsal ponto-mesencephalic brainstem. Taken together, our analysis of subcortical and cortical grey matter in the dystonic phase of X-linked dystonia-parkinsonism showed that (i) the striosome-enriched rostral striatum was most severely affected; and (ii) cortical thickness was only reduced in those regions that predominantly have anatomical connections to striosomes. Moreover, the cerebellum may be implicated in both disease-related and compensatory changes, highlighting the significance of the cerebellum in the pathophysiology of dystonia.
Journal of Medicine, University of Santo Tomas, Dec 31, 2021
Rationale: Entrapment neuropathies are peripheral nerve disorders at specific anatomical location... more Rationale: Entrapment neuropathies are peripheral nerve disorders at specific anatomical locations. They may be caused by trauma in a manner of sprains or bone fracture, but it is often caused by repetitive insults or compression of nerves as they travel through a narrow anatomic space. Pregnancy and pre-existing comorbidities such as diabetes, obesity, cancer, or autoimmune diseases may also cause nerve entrapment. Objective: To highlight the case of a 52-yearold female developing right foot dysesthesia and weakness after continuous restraint strapping from her previous hospitalization. Case: Here we have the case of a 52-year-old Filipino female consulted because of right foot dysesthesia, allodynia, and mild weakness. She had a history of bipolar disorder and recent onset of acute psychosis and overdosing with her irregularly taken maintenance olanzapine tablets. She was put on restraint strapping of the right lower limb in her one-week hospital stay. This resulted in developing restraint marks on her right ankle accompanied by difficulty walking on heels and toes, spontaneous dysesthesia, and touch allodynia of her entire right foot. An electrodiagnosis yielded right lower limb focal neuropathies involving the right fibular nerve, right tibial nerve, right superficial fibular, and right sural nerves. The prescribed amitriptyline and gabapentin for 6 months led to gradual improvement of neuropathic pain. Discussion and Summary: Our case exemplifies focal limb neuropathies from entrapment due to restraint strapping. Electrodiagnostic confirmation of neuropathies of the same limb sensory and motor nerves was mandated to corroborate clinical neuropathic pain and after ruling out other causes of entrapment neuropathies. Prolonged use of neuropathic pain medications were needed to attain relief in this present case. Restrictive strapping is an iatrogenic cause of entrapment neuropathy that is preventable, had there been proper medical attention applied.
medRxiv (Cold Spring Harbor Laboratory), Jan 13, 2022
Medicine, case reports and study protocols, Jun 1, 2021
Parkinsonism & Related Disorders, Oct 1, 2020
Journal of Medicine, University of Santo Tomas, May 31, 2020
Journal of Medicine, University of Santo Tomas, Jan 31, 2020
Journal of Medicine, University of Santo Tomas, Sep 1, 2017
Neurosarcoidosis is a rare or misdiagnosed disease that can be masked in a case with fl eeting ne... more Neurosarcoidosis is a rare or misdiagnosed disease that can be masked in a case with fl eeting neurologic defi cits, especially craniopathy. We present a 26-year-old Chinese-Filipino male who presented with recurrent facial neuropathy that was heralded by fl eeting blurring of vision bilaterally. He was apparently responsive to corticosteroids (intravenous and oral methylprednisolone) from initiation to date. During the course, he also noted selective weakness of the right fi nger fl exors. Nodules in the face eventually appeared that led to a biopsy disclosing a noncaseating granuloma. Apart from electrodiagnostic tests, a supportive diagnostic test for sarcoidosis was the presence of lymphadenopathies on his chest noted on Computed Tomography (CT) scan. Cerebrospinal fl uid (CSF) and brain Magnetic Resonance Imaging (MRI) tests were not yielding. To our knowledge, this was the fi rst reported Chinese-Filipino case of neurosarcoidosis involving cranial and peripheral nerves.
Journal of the Neurological Sciences, Oct 1, 2017
At the end of the 1970s, dystonia was seen as something peculiar, balancing on the edge between o... more At the end of the 1970s, dystonia was seen as something peculiar, balancing on the edge between organic disorder and psychiatric condition. The everlasting enigma of dystonia has been breeched for the first time by David Marsden, who attributed the clinical syndrome to a disorder of basal ganglia functioning. As he postulated in the seminal work regarding the natural history and clinical presentation of dystonia, dystonia is a syndrome of sustained involuntary muscle contraction, frequently causing twisting or repetitive movements or abnormal postures. Although a new definition of dystonia has been recently adopted, Marsden’s concept is still a cornerstone of it. One can undoubtedly characterise the dystonic movement as a result of volitional (albeit unconscious) motor action. There is enough evidence that dystonia is the “normal” motor action abnormally accompanied by the action of antagonists, or by the co-contractions of inappropriate muscles, and by the defective reciprocal inhibition of other muscles. As a result, there is a dystonic movement or dystonic posture appearing as final vector of that deviant muscle activity. Dystonia does not look like a chaotic medley of contractions and muscle relaxation, as do a majority of other hyperkinetic movement disorders. Dystonia rather looks like a highly (albeit aberrantly) organised motor performance. The motor action seen in patients with dystonia is apparently not a result of several abnormal contractions or muscle jerks. It is complex dyskinesia, which only sometimes changes character over time. Named “a shadow of movement” by Rondot more than 20 years ago, dystonia was proposed as a primitive “kind of movement”, similar to that which can still be seen in other primates. The motor action itself was seen as a “dystonic way back” in the phylogenetic history of motor action. In Rondot’s view, dystonia is something that is constantly present in the mature human motor system, but which can only be seen in particular circumstances, for instance in the case of basal ganglia lesion (or other basal ganglia involvement, as in the case of idiopathic dystonia). Nevertheless, all recent and current physiological indices are only pieces of a puzzle. We believe that once completed, this jigsaw will show idiopathic dystonia in the frame of defective programming and organisation of motor action due to defective somatosensory flow consequent to defective sensorimotor integration or brain plasticity, in which the movement itself is perfectly performed.
Cambridge University Press eBooks, Jun 4, 2018
Journal of Medicine, University of Santo Tomas, 2021
Based largely on interest and preference, there are physician-scientists who are engaged in the d... more Based largely on interest and preference, there are physician-scientists who are engaged in the dual work of being a clinician and researcher. Some of them have the added responsibility of also being academicians or members of medical faculties. The article, “Physician as a Clinician, Researcher and Academician” in this JMUST issue demonstrates the importance of organizational support and collaboration for physicians. The doctor has multiple roles to navigate through three settings: clinics, research centers, and classrooms to fulfill the mission of better public health. Research and dissemination of findings through publication are almost sine qua non when the physician blends the roles of clinician, researcher, and academician. Within the purview of translational research, the clinician is informed and applies the knowledge base for better patient care.
Uploads
Papers by Raymond L Rosales