Jaw-opening Dystonia Research Articles

OROMANDIBULAR DYSTONIA: PREVALENCE, CLINICAL AND DEMOGRAPHIC DATA, THERAPEUTIC STRATEGIES OUT-COME FOR HUNDRED PATIENTS IN SANA’A CITY, YEMEN

Background and aims: Dystonia is a movement disease characterized by persistent, uncontrollable muscle contractions that often lead to abnormal postures. The tongue, jaw, and mouth are all affected by OMD, which is an uncommon focal dystonia. OMD is a rare public health problem that takes time to diagnose and treat because it is frequently identified as psychogenic. This study sought to ascertain the frequency, demographics, clinical features, and treatment outcomes of patients with mandibular dystonia (OMD) in Sana'a, Yemen. Methods: A prospective cross-sectional study was conducted; the study included 100 Yemeni adults attending the Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, Sana'a University Clinics and Departments of Oral, Maxillofacial and Neurosurgery at Kuwait University Hospital and some private centers for maxillofacial medicine and neurosurgery in the city of Sana’a during the year 2022. The selected patients were complaining of contraction or involuntary movement of the masticatory, lingual and/or lower facial muscles. Age, gender, age at onset of illness, duration of illness, personal habits, type of OMD, previous and current treatments, and their outcomes were recorded on a standard, pre-designed questionnaire. Results: The incidence rate of OMD is 19/100,000/year. Most of the patients (92%) are male while only 8% are female. The first episode onset is after stress (29%), 11% after illness, 6% after dental treatment, and 48% without causes. Jaw deviation dystonia was dominant at 65%, followed by jaw closing dystonia (42%), jaw protrusion dystonia (29%), and jaw opening dystonia (27%). After current treatment out-come, there was improvement on ability to eat ( from 12% to 24%, p=0.02), to speak (from 25% to 43%, p=0.007), the rate of no pain raised from 46% to 57%, the rate of no discomfort raised from 21% to 34% (p=0.04) and the score ≤ 5 of OMD raised from 47% to 72% (p=0.0003). Conclusion: The incidence of OMD in Sana’a city is remarkably high, predominantly male, and peaks at 30, 40, and 50 years of age. Jaw deviation dystonia was the dominant type followed by jaw closing dystonia. After the current treatment outcome, the ability to eat has improved, the rate of pain and discomfort has decreased. Peer Review History: Received: 25 February 2023; Revised: 17 March; Accepted: 28 April 2023, Available online: 15 May 2023 Academic Editor: Dr. Sally A. El-Zahaby, Pharos University in Alexandria, Egypt, sally.elzahaby@yahoo.com Received file: Reviewer's Comments: Average Peer review marks at initial stage: 5.5/10 Average Peer review marks at publication stage: 7.0/10 Reviewers: Dr. Bilge Ahsen KARA, Ankara Gazi Mustafa Kemal Hospital, Turkey, ahsndkyc@gmail.com Dr. Ogbonna B. Onyebuchi, Nnamdi Azikiwe University, Awka, Nigeria, summitpharm@yahoo.com

Paraneoplastic Neurologic Syndromes with ANNA-2/anti-Ri: a Contrasting Story of Two Cases (P5-5.026)

Paraneoplastic Neurologic Syndromes with ANNA-2/anti-Ri: a Contrasting Story of Two Cases (P5-5.026)

Oromandibular Dystonia: Clinical and Demographic Data from Eight-Two Patients.

This study aimed to determine the demographic and clinical characteristics of patients with oromandibular dystonia (OMD). Dystonia is a movement disorder characterized by sustained involuntary muscle contractions that often cause abnormal postures. OMD is a rare focal dystonia that affects the tongue, jaw, and mouth. OMD, which is a rare public health problem, is often recognized as psychogenic and there are delays in its diagnosis and treatment. Patients with OMD, both isolated and combined, followed at our Movement Disorders Outpatient Clinic between 2004 and 2021 were enrolled in this study. Age, sex, age at onset, and disease duration were recorded. The type of OMD, affected muscles, etiologies of accompanying neurological disorders, and treatment were noted. A total of 82 patients (44 women, 38 men) were included in this study. Among these, 39 patients had isolated OMD, and 43 patients had either segmental or generalized dystonia. Seven patients reported a family history of dystonia. Only nine patients reported a sensory trick. The average disease duration was 6.01 ± 3.73 (range, 1-29) years, and the average age at onset was 43.34 ± 18.24 (range, 1-78) years. The disease etiology was unknown (idiopathic) in most patients. Fifteen patients reported task-specific dystonia. The most common type of dystonia was jaw-opening dystonia. OMD is focal dystonia that significantly affects the quality of life. This study adds more data to the literature by defining the clinical features of this rare disorder and draws attention to this neglected type of dystonia.

Effects of Botulinum Toxin Therapy on Health-Related Quality of Life Evaluated by the Oromandibular Dystonia Rating Scale.

Oromandibular dystonia (OMD) refers to a focal dystonia in the stomatognathic system. Health-related quality of life (HRQoL) in isolated dystonia is associated with non-motor symptoms such as depression, anxiety, and pain, as well as motor symptoms. To evaluate HRQoL in patients with OMD, the therapeutic effects of botulinum neurotoxin (BoNT) therapy were assessed using a recently developed and validated comprehensive measurement tool called the Oromandibular Dystonia Rating Scale (OMDRS). Altogether, 408 patients (jaw closing dystonia, n = 223; tongue (lingual) dystonia, n = 86; jaw opening dystonia, n = 50; jaw deviation dystonia, n = 23; jaw protrusion dystonia, n = 13; and lip (labial) dystonia, n = 13) were evaluated at baseline and after the end of BoNT therapy or in a stable status. The total OMDRS score reduced significantly from 149.1 to 57.6 (p < 0.001). Mean improvement was 63.1%. All examiner-rated subscales (severity, disability, and pain) and patient-rated questionnaire scores (general, eating, speech, cosmetic, social/family life, sleep, annoyance, mood, and psychosocial function) were significantly lower at the endpoint than at baseline (p < 0.001). The BoNT injection had a highly positive impact on patient HRQoL, and the OMDRS could evaluate both motor phenomena and non-motor symptoms.

Development and Validation of a Disease-Specific Oromandibular Dystonia Rating Scale (OMDRS).

Background: Oromandibular dystonia manifests with sustained or task-specific contractions of the masticatory, tongue, and/or other muscles in the stomatognathic system. Since its symptoms can vary, it has been difficult to objectively measure disease severity and post-treatment changes.Objective: To develop and validate a comprehensive measurement tool for oromandibular dystonia.Methods: An examiner-rated scale included three subscales for severity, disability, and pain, modified specifically for oromandibular dystonia from the Toronto Western Spasmodic Torticollis Rating Scale-2. To evaluate the severity of each subtype of oromandibular dystonia, four of the six items were selected according to the subtype (jaw closing dystonia, tongue dystonia, jaw opening dystonia, jaw deviation [protrusion] dystonia, and lip dystonia). A patient-administered questionnaire based on clinical features and other relevant aspects associated with oromandibular dystonia was developed, which included five subscales: general, eating, speech, cosmetic, and social/family life. The questionnaire, examiner-rated scale, and four subscales (sleep, annoyance, mood, and psychosocial functioning) of the Cervical Dystonia Impact Profile-58 were combined to construct the oromandibular dystonia rating scale (OMDRS). The reliability and validity of the scale were assessed using clinimetric testing.Results: Six hundred and eighteen patients with oromandibular dystonia (394 women and 224 men; mean age, 51.7 years) were evaluated by the OMDRS. The overall OMDRS showed high-level internal consistency measured by Cronbach's alpha (0.95) with a logical factor structure. Cronbach's alpha for the subscales was satisfactory to excellent, ranging from 0.72 to 0.94. All items revealed acceptable inter-rater reliability (kappa > 0.4, interclass correlation coefficient > 0.6). Repeated ratings of videotapes revealed acceptable intra-rater reliability for all items (kappa > 0.76, interclass correlation coefficient > 0.86). Test-retest reliability showed a significant (p < 0.001) correlation efficiency. The OMDRS showed significant (p < 0.001) convergent and discriminant validity and significant (p < 0.001) sensitivity to changes after botulinum toxin therapy.Conclusion: The OMDRS can be useful for the comprehensive evaluation of disease severity, disability, psychosocial functioning, and impact on the quality of life as well as therapeutic changes in patients with oromandibular dystonia.

Novel PANK2 mutation identified in patient with pantothenate kinase-associated neurodegeneration

Introduction. Pantothenate kinase-associated neurodegeneration (PKAN) is a rare, recessively inherited disorder caused by mutations in the pantothenate kinase 2 (PANK2) gene on chromosome 20p13. The objective of this report is to present a patient with atypical PKAN with the novel heterozygous PANK2 mutation. Case outline. We present a 32-year-old female who had disease onset at the age 20 (depression, speech, chewing problems and backward falls) with progressive course. Neurological examination revealed hypomimia, risus sardonicus, dysphagia, tachylalia and severe dystonic dysarthria, moderate arms, legs, and jaw-opening dystonia, postural instability, urge incontinence, and decreased visual acuity. Brain magnetic resonance imaging revealed iron accumulation in the bilateral globus pallidus and putamen (?eye-of-the-tiger?), a radiological finding pathognomonic for PKAN. Genetic analysis revealed known mutation p.T528M (c.1583C&gt;T) in exon 6, and novel p.Y405D (c.1213T&gt;G) in exon 3 of the PANK2 gene. In silico analyses strongly suggested this mutation to be pathogenic. Conclusion. We report a patient with PKAN, and novel substitution p.Y405D (c.1213T&gt;G) in PANK2 that has not been previously described in PKAN patients.

Severe Jaw-Opening Dystonia as an Unusual Manifestation of Levodopa-Related Wearing-Off in Parkinson's Disease, and Successful Treatment With Botulinum Toxin Injection.

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Clumsiness, stuttering and progressive jaw opening dystonia

Clumsiness, stuttering and progressive jaw opening dystonia

Computer-Aided Design/Computer-Assisted Manufacture-Derived Needle Guide for Injection of Botulinum Toxin into the Lateral Pterygoid Muscle in Patients with Oromandibular Dystonia.

To evaluate the effectiveness and safety of botulinum toxin administration into the inferior head of the lateral pterygoid muscle of patients with jaw opening dystonia by using a computer-aided design/computer-assisted manufacture (CAD/CAM)-derived needle guide. A total of 17 patients with jaw opening dystonia were enrolled. After the patient's computed tomography (CT) scan was imported and fused with a scan of a plaster cast model of the maxilla, the optimal needle insertion site over the lateral pterygoid muscle was determined using the NobelClinician software. A total of 13 patients were injected both with and without the guide, and 4 patients underwent guided injection alone. The therapeutic effects of botulinum toxin injection and its associated complications were statistically compared between the guided and unguided procedures using paired t test. Botulinum toxin therapy was performed 42 and 32 times with and without the guides, respectively. The needle was easily inserted without any complications in all procedures. There was a significant difference (P < .001) between the mean comprehensive improvements observed with (66.3%) and without (54.4%) the guides. The findings suggest that the use of needle guides during the injection of botulinum toxin into the inferior head of the lateral pterygoid muscle is very useful for aiding the accurate and safe administration of botulinum toxin therapy for jaw opening dystonia.

Systematic review of botulinum toxin treatment for oromandibular dystonia

Oromandibular dystonia (OMD) is an isolated focal dystonia that affects the muscles of the jaw, lower face and tongue. It is a rare disorder but is associated with significant impairment in quality of life. Treatment with oral medications has not been successful. Surgical interventions, such as deep brain stimulation, may be of benefit but have not been adequately evaluated. Currently, botulinum toxin (BoNT) injections are regarded as the treatment of choice for OMD. However, the evidence supporting this is not available. Most studies are open label, observational studies, longitudinal clinical experience, case reports or retrospective analysis. From the available studies, OMD is responsive to appropriately targeted BoNT injections. Jaw closing dystonia responds the most robustly. Jaw opening dystonia is more complex to inject, but clinical experience is consistent with benefit. Lingual dystonia is the most difficult because injections into tongue muscles frequently give rise to dysphagia. More controlled studies are required to establish BoNT as an effective treatment for OMD.

Sensory trick splint as a multimodal therapy for oromandibular dystonia

PurposeMany patients with oromandibular dystonia, which is characterized by involuntary masticatory, lower facial, and/or tongue muscle contractions, experience relief of symptoms through sensory tricks such as eating chewing gum or candy. The aim of this study was to identify the factors influencing the effects of splints in patients with oromandibular dystonia. MethodsOcclusal splints were inserted in 128 patients (89 women, 39 men) with oromandibular dystonia (102 with jaw closing dystonia, 20 with lingual dystonia, 5 with jaw deviation dystonia, 4 with jaw opening dystonia, 3 with lip dystonia, and 2 with jaw protrusion dystonia). Patients who showed improvement with the use of splints and continued to wear them for at least 3 months were defined as responders. In contrast, patients who showed little or no effect and/or were unable to insert splints were defined as non-responders. Differences in demographic and clinical data were statistically compared between responders and non-responders. ResultsNinety-eight patients (76.6%) were responders (subjective improvement: 30.5%). Thirty patients (23.4%) were non-responders (subjective improvement: 7.2%). The responders were significantly older than the non-responders (53.8 years vs 47.0 years; p<0.05). Patients with jaw closing dystonia showed the most favorable results. The proportion of patients with sensory tricks was significantly higher in responders than in non-responders (66.3% vs 26.7%; p<0.05). ConclusionsThe sensory trick splint is especially helpful for patients with jaw closing dystonia. It is useful, although partially effective, as an alternative therapy in patients for whom other therapies have been unsatisfactory.

Psychogenic (Functional) Jaw-Opening Dystonia: Three Case Reports and a Comparison of Symptomatic Jaw-Opening Dystonia Associated with Organic Causes in the Literature

Background: Jaw-opening dystonia is very rarely reported, and involuntary jaw-opening dystonia as an initial manifestation of psychogenic (functional) movement disorder has not yet been reported. This study aimed to report unusual cases of psychogenic (functional) jaw-opening dystonia and to compare the clinical patterns between organic and psychogenic (functional) jaw-opening dystonia. Method: We enrolled three psychogenic (functional) movement disorder patients presenting involuntary severe jaw-opening dystonia as an initial manifestation. Moreover, we review previously reported cases and analyze the clinical pattern of organic psychogenic (functional) jaw-opening dystonia in comparison with our cases. Results: Among 10 cases, including our cases, the most common pattern of organic jaw-opening dystonic symptoms was the sustained pattern. By contrast, all three patients with psychogenic (functional) jaw-opening dystonia presented with a paroxysmal pattern. The major neuro-radiologically associated localizations of organic jaw-opening dystonia were the cerebellum and basal ganglia. Sensory feedback or “sensory tricks” were only observed in organic jaw-opening dystonia. Conclusion: The results of this clinically investigative study may provide support for the differential diagnosis of jaw-opening dystonia between organic and psychogenic (functional) etiologies. Additionally, if paroxysmal jawopening dystonia combined with inconsistent, incongruous hyperkinetic movement symptoms is present, diagnosis of a psychogenic (functional) movement disorder should be considered.

Spectrum of Abnormal Movement in a Cohort of Neuro-Wilson Patients with Radiological Associations

Background: Disorders of movement are important features of Neuro-Wilson’s disease (NWD) and their recognition helps in early diagnosis. We studied the various types of movement disorders including any novel phenomenology found in our cohort of NWD, along with radiological correlations. Method: A total of 129 consecutive patients of WD (M:F) were examined in Movement Disorders clinic of a tertiary care neurological institute at Kolkata, India. A semi-structured interview and examination determined the various types of movement disorders detected, after proper informed consent. Neuro-imaging (MRI of 1.5 Tesla system) was carried out whenever possible. Results: The common movement disorders were dystonia (91.8%), Parkinsonism (83.72%), and tremor (53.49%). Others were movement induced focal myoclonus (12.4%), ataxia (11.63%), choreo-athetosis (15.5%). The less frequent movement disorders were akathisia (5.2%) and tics disorder (5.42%) and oromandibular dyskinesias (2.33%). MRI lesions were found to be associated with jaw opening dystonia (caudate), neck dystonia (putamen and pons), truncal dystonia (caudate, globus pallidus and cortical atrophy), appendicular dystonia (caudate and putamen), Parkinsonism (mid-brain), postural tremor (caudate and putamen), tics and akathisia (mid-brain and pons in both). Conclusion: WD is associated with a variety of common movement disorders such as dystonia, Parkinsonism and tremor. The less frequent movement disorders were focal myoclonus, stereotypes, tics disorders and orofacial dyskinesia . Radiological lesions can be found in association with majority of the movement disorders except in few cases where functional imaging studies may help.

Atypical presentation of psychogenic movement disorder with jaw-opening dystonia: two cases reports

Atypical presentation of psychogenic movement disorder with jaw-opening dystonia: two cases reports

Successful treatment of open jaw and jaw deviation dystonia with botulinum toxin using a simple intraoral approach

Oromandibular dystonia (OMD) is a focal dystonia that involves the mouth, jaw, and/or tongue. It can be classified as idiopathic, tardive dystonia or secondary to other neurological disorders and subdivided into jaw opening, jaw closing, jaw deviation and lip pursing. The muscles involved in jaw opening dystonia are usually the digastrics and lateral pterygoids. It is known that the lateral pterygoids may be approached both internally and externally. The external approach is the most common; however neurologists experienced in treating patients with botulinum toxin can safely and with no extra cost perform the intraoral procedure. We report our experience in the treatment of jaw opening and jaw deviation dystonia using the intraoral injection approach. Eight patients were selected from the University of Florida with a clinical diagnosis of open jaw/jaw deviation dystonia. All of them were injected with onabotulinum toxin A using the internal approach and the clinical global impression scale was applied. The mean age of the patients was 67 (standard deviation [SD] 10.2) years, with a disease duration of 10.2 (SD 7.7) years and the mean distance they traveled to our institution was 448km (278 miles). After treatment, six patients scored as very much improved in the clinical global impression scale and two patients scored as much improved. Only one patient reported an adverse event of nasal speech following one of the injections that improved after 4 weeks. Botulinum toxin injections for open jaw/jaw deviation dystonia can be safely performed with the intraoral approach without the need of special devices other than electromyography.

Jaw-Opening Dystonia: Quality of Life after Botulinum Toxin Injections

The objective of this study was to investigate quality-of-life outcomes in patients with jaw-opening oromandibular dystonia who had received treatment with botulinum neurotoxin injections. The Glasgow Benefit Inventory (GBI) was used as a post-intervention questionnaire to measure patient benefit. Twenty-five questionnaires were sent to patients. Of the 12 patients who returned the form (48% response rate), the mean scores for the general GBI subscore (p = 0.001), the social support GBI subscore (p = 0.031), and the physical health GBI subscore (p = 0.002) demonstrated statistically significant benefit from the injections. No scores demonstrated a negative impact. Botulinum neurotoxin injections were demonstrated to benefit the quality of life in patients suffering from jaw-opening oromandibular dystonia.

Anti–N-methyl-D-aspartate Receptor Encephalitis

Anti–N-methyl-d-aspartate (anti-NMDA) receptor encephalitis is a treatable paraneo-plastic disorder predominantly affecting young women. It is characterized by a combination of psychotic encephalopathy, seizures, and abnormal movements of the trunk and face, particularly in the form of jaw dystonia. Enhanced awareness of the typical presentation can increase the index of suspicion and facilitate initiation of appropriate treatment. A previously healthy 26-year-old African American woman presented to the emergency department after an acute episode of psychotic behavior in which she was described as becoming abruptly agitated and restless. Over the next few days, she developed seizures and sustained impairment of consciousness for which she required intubation and intensive care monitoring. She showed intermittent agitation with screaming and crying spells. Electroencephalography revealed bilateral independent temporal epileptiform discharges, which prompted treatment with phenytoin. On neurological examination, she was awake but unresponsive to verbal or noxious stimulation. Several episodes of jaw-opening dystonia, paroxysmal opisthotonus, and catatonic postures were observed (Figure 1A and B, video [http://www.archneurol.com]). Figure 1 Jaw-opening dystonia (A) and opisthotonic posture (B) are observed. C, A fluid-attenuated inversion recovery sequence of an axial brain magnetic resonance image shows symmetric hyperintensities in the cerebellar hemispheres (arrows). Analysis of cerebrospinal fluid showed lymphocytic pleocytosis (white blood cell count, 200/µL), with normal glucose and protein levels. Results from cytology, Gram stain, cultures, and polymerase chain reaction for herpes simplex virus, varicella zoster virus, Epstein-Barr virus, and West Nile virus in cerebrospinal fluid were negative. Brain magnetic resonance imaging disclosed hyperintensities in both cerebellar hemispheres (Figure 1C). Results for human immunodeficiency virus, rapid plasma reagin, serum cultures, autoimmune panel, and thyroid-stimulating hormone, free thyroxine, folic acid, and B12 levels were within normal limits. Results from the following paraneoplastic antibody tests were negative: antineuronal nuclear, cytoplasmatic Purkinje cell, amphiphysin, collapsing-response mediator protein type 5, calcium channel, acetylcholine receptor ganglionic neuronal, antiglial nuclear, and voltage-gated potassium channel. Using human embryonic kidney 293 cells transfected with NR1/NR2 heteromers,1 antibodies against NMDA receptors were found in cerebrospinal fluid (serial dilutions; titer, 1:160) and serum (titer, 1:40). Although initial pelvic computed tomographic and ultrasonographic results were unrevealing, a pelvic magnetic resonance image demonstrated a right 9-mm ovarian mass (Figure 2A), which proved to be a teratoma on histopathological analysis (Figure 2B). Surgical teratoma excision and intravenous methylprednisolone sodium succinate led to noticeable improvement in function over the next few days. Five weeks after this treatment, the patient had returned to work. Figure 2 Imaging and histopathological findings. A, A T1-weighted magnetic resonance image of the pelvis shows a 9-mm high-signal mass in the right ovary, suggestive of a small teratoma (arrow). B, Hematoxylin-eosin staining of the ovarian mass demonstrates typical ...

Use of an oral sensory feedback device in the management of jaw-opening dystonia

Use of an oral sensory feedback device in the management of jaw-opening dystonia

Familial idiopathic basal ganglia calcification: a challenging clinical–pathological correlation

Sir, Familial idiopathic basal ganglia calcification (FIBGC) is characterized by brain calcium deposition and variable combinations of movement disorders, gait impairment, and neuropsychiatric symptoms [1-3, 5-7]. A locus was mapped on chromosome 14 [2], but it fails to account for disease in some families [7]. Penetrance estimates are hampered by inconsistent clinical-radiological correlation, and few detailed pathological reports are available [4, 7]. Herein, we provide clinical, radiological and pathological studies of a patient with FIBGC. We previously reported this family, including one autopsy study [4, 7]. The patient signed informed consent. A right-handed male (patient III-3 in [7]) came to our attention at age 76 with a 50-year history of trunk, upper extremities and oral abnormal movements. Motor symptoms began with writing difficulties, followed by right-predominant abnormal movements of both shoulders. At age 50, he developed progressive speech difficulties with mild memory and gait impairment. Six first-degree and three second-degree relatives had similar symptoms including generalized, oromandibular, axial, limb and cervical dystonia, chorea, postural tremor and ataxia (reported in [7]). The patient had mild recall impairment, speech-induced jaw-opening dystonia, trunk and right-predominant upper extremities chorea, right shoulder postural dystonia, and writer's cramp. Genetic testing was negative for Huntington's disease. Brain CT-scan showed calcification of the basal ganglia, subcortical white matter, thalamus, and cerebellum (Figure 1). Figure 1 Brain axial CT-scan shows third and lateral ventricles enlargement and severe calcification of the cerebellar hemispheres and vermis (a,b), striatum, globus pallidus and thalamus (b,c), and subcortical white matter and occipital cortex (a-d). Basal ganglia ... Over the next five years, the patient became severely dysarthric and unstable with falls. Upper extremities and trunk chorea and dystonia remained unchanged, whereas jaw-opening dystonia worsened. He scored 21/26 on the Mini Mental Status Examination (unable to write or draw), missing points on attention span and recall. The patient subsequently developed severe cognitive impairment and behavioral troubles with agitation and aggressiveness. He became unable to stand, chew or speak, lost 30kg over two years, and died at age 85. The fixed left hemibrain weighed 520g. There was mild frontal-predominant atrophy with enlarged lateral ventricles, and cerebellar atrophy. Brain arteries showed severe atherosclerosis. There was gray discoloration and gritty consistency of the posterior periventricular region, globus pallidus, putamen and anterior thalamus, and mild atrophy of the caudate nucleus (Figure 2a). The cerebellum had yellow-red discoloration and gritty consistency of deep white matter and dentate nucleus region. Figure 2 Macroscopic view (a) shows brown discoloration of globus pallidus (arrow), which had a gritty consistency at autopsy. On histology, von Kossa calcium staining (b) and hematoxylin-eosin staining (c-l) show widespread calcification of cerebellum deep regions ... There was striking vascular and parenchymal mineralization (Figure 2b-l) that stained positive for calcium (Figure 2b). In the cortex, small vessel calcific vasculopathy was prominent in lower cortical layers and at the grey-white junction in the depths of the sulci. Parenchymal calcification was patchy and multifocal in deep subcortical and posterior periventricular regions, putamen, globus pallidus, anterior thalamus, and in the visual cortex. There was massive cerebellar calcification in the hemispheres (cortex and white matter) and in the dentate nucleus. Even in severely affected areas, there was no significant neuronal loss. Mild Alzheimer pathology and amyloid angiopathy were present. There were ischemic changes in subcortical areas and numerous microinfarcts in the cortex and basal ganglia. Overall, the pathology was similar to that of our previous autopsied patient from the same family [4, 7]. Our observation highlights the difficulties in correlating the clinical, radiological and pathological features in FIBGC. Reasons for this include that: a) many family members have widespread calcification without symptoms [7], b) radiologic asymmetry does not always match that of symptoms, c) ataxia is rare despite common severe cerebellar involvement, and d) there is no significant neuronal loss even in severely affected areas. Although basal ganglia and subcortical/periventricular white matter involvement may explain movement disorders and cognitive impairment, the mechanism of neuronal dysfunction remains elusive. Extensive blood vessel and perivascular calcification may suggest a chronic ischemic mechanism leading to neuronal dysfunction only in susceptible brain regions/individuals. Chronic low-grade inflammation has been suggested to favor calcification, a hypothesis that gained support from the report of reactive astrocytes and microglia overexpressing inflammatory molecules around calcified areas [4]. However, using HLA-DR and GFAP immunostaining in our patient, we were unable to demonstrate activated microglia and reactive astrocytes. Alternatively, calcium deposition may alter glial cells metabolism and secondarily impair neuronal function, or only represent a by-standing phenomenon of a yet undefined patho-mechanism involving genetically-determined age-related neuronal dysfunction.

First case of X‐linked dystonia‐parkinsonism (“Lubag”) to demonstrate a response to bilateral pallidal stimulation

"Lubag" or X-linked dystonia-parkinsonism (XDP) is a genetic syndrome afflicting Filipino men. Intracranial surgical procedures for Lubag have been unsuccessful. We report a 45-year-old Filipino male with genetically confirmed XDP who underwent bilateral pallidal deep brain stimulation (DBS) surgery. The patient started to exhibit improvement on initial programming, most notably of his severe jaw-opening dystonia. At 1-year follow-up, his Burke-Fahn-Marsden dystonia score and motor Unified Parkinson's Disease Rating Scale score were improved by 71% and 62%, respectively, with the stimulators on compared to stimulators off state. Bilateral pallidal DBS may be a viable option for Lubag patients with medically refractory symptoms.