Summary:Purpose: Reversible cerebral vasoconstriction has been hypothesized to be the etiology of seizures due to hypercalcemia, but angiographic studies documenting vasoconstriction have not previously been available.Methods: We present a 43-year-old woman who had frequent seizures that later evolved to status epilepticus with marked hypercalcemia at the time of the seizures.Results: Magnetic resonance imaging (MRI) of the patient's brain revealed high signal changes in T 2 -weighted imaging, fluorescence-attenuated inversion recovery (FLAIR), and diffusion-weighted imaging (DWI) over the bilateral occipital and thalamic areas. Cerebral angiography showed blood vessels narrowing, disappearing altogether over the right posterior cerebral artery (PCA) branch, which is compatible with vasoconstriction. Vasoconstriction caused the MRI high signal in the occipital area, which was associated with subsequent periodic lateralized epileptic discharges. The patient's clinical condition improved with management of seizures and hypercalcemia. A second brain MRI 2 weeks later revealed complete resolution of the high-signal lesions. Follow-up cerebral angiography study also showed total recovery of vasoconstriction.Conclusions: The sequence of events suggests the hypothesis that reversible cerebral vasoconstriction may play a role in hypercalcemia-induced seizures. Key Words: SeizureHypercalcemia-Vasoconstriction.Hypercalcemia can cause drowsiness, lethargy, weakness, confusion, and coma, but rarely causes seizures. Neuronal membrane excitability changes (1,2), hypertensive encephalopathy, and vasoconstriction induced by hypercalcemia all have been hypothesized to be the etiologies of seizures (1,3), but vasoconstriction during hypercalcemic seizures has not yet been reported. We present a patient with status epilepticus, caused by breast carcinoma-induced hypercalcemia. Serial brain magnetic resonance imaging (MRI) and cerebral angiography studies showed reversible occipital high-signal abnormalities and transient cerebral vasoconstriction. These findings suggest that vasoconstriction is a contributing factor to hypercalcemia-related seizures. CASE REPORTA 43-year-old right-handed housewife had low back pain and osteoporosis for several years. She was brought to the emergency room (ER) for frequent seizures. The paAccepted January 28, 2004. Address correspondence and reprint requests to Dr. S-L. Lai at Department of Neurology, Kaohsiung Chang-Gung Memorial Hospital, Kaohsiung, Taiwan, 123 Ta-Pei Rd. Niao-Sung Hsiang, Kaohsiung County, Kaohsiung, Taiwan. E-mail: carlos@adm.cgmh.org.tw tient was unconscious, and frequent partial seizures with secondary generalization were noted while she was in the ER. Laboratory evaluation disclosed severe hypercalcemia with serum total calcium of 15.5 mg/dl. Hydration with normal saline at 100 ml/h and magnesium sulfate were administered as treatment for hypercalcemia. Diazepam (DZP) and phenytoin (PHT) were given for the status epilepticus. Physical examination detected a left breast mass,...

Objective: Parkinson disease (PD) is a debilitating neurodegenerative disease. Caring for an individual with PD can have a variety of negative physical and psychological effects on caregivers which may challenge their ability to continue in their caretaking role. The aim of this study was to assess the prevalence and associated factors of depressive disorders in caregivers of individuals with PD using standardized instruments. Methods: This study used a cross-sectional design with consecutive sampling. Study participants were recruited from the neurological ward or neurological outpatient clinic of a medical center from August 2018 to July 2019. Caregivers of persons with PD were enrolled and assessed using the Mini International Neuropsychiatric Interview, Hamilton Depression Rating Scale, Hamilton Anxiety Rating Scale, Beck Hopelessness Scale, Brief Fatigue Inventory, Connor-Davidson Resilience Scale, and Big Five Inventory-10. Results: Of the 162 caregivers that completed the study, 67.3% (n = 109) were females. The most common psychiatric diagnosis was depressive disorder (11.1%), followed by insomnia disorder (7.4%) and anxiety disorder not otherwise specified (4.3%); 28% of the caregivers had a psychiatric diagnosis. Using logistic regression analysis, it was found that duration of caregiving (odds ratio [OR] = 1.28; 95% CI, 1.05-1.58), severity of anxiety (OR = 1.86; 95% CI, 1.36-2.53), and severity of fatigue (OR = 1.08; 95% CI, 1.01-1.16) were 3 significant associated factors for the development of depression. Conclusion: Depression was the most prevalent psychiatric diagnosis in caregivers of people with PD. Early diagnosis of these caregivers is crucial to the offering of suitable support and treatment and might improve caregivers’ quality of life.

BackgroundVacuolar protein sorting 35 (VPS35) was recently reported to be a genetic cause for late-onset autosomal dominant Parkinson’s disease (PD). However, VPS35 mutations are rarely reported in Asian populations. Herein, we report the first Taiwanese family with the pathogenic VPS35 p.D620N mutation, including one patient treated successfully with subthalamic nucleus deep brain stimulation (STN-DBS).Case presentationA 61-year-old woman presented with progressive left hand resting tremor at the age of 42. Neurological examinations revealed mask face and akinetic-rigidity over left extremities. She showed a good response to levodopa treatment, and her unified Parkinson’s disease rating scale (UPDRS) motor scores improved from 42 to 15 under the levodopa equivalent dose of 1435 mg/day. She developed peak-dose dyskinesia and motor fluctuation seven years after the onset of symptoms, and received bilateral STN-DBS at the age of 55. Stimulation led to a marked improvement in her motor symptoms with a 37% improvement in the UPDRS motor score during the OFF period five years after surgery. The patient’s mother and three siblings were also diagnosed with PD in their forties, following an autosomal-dominant inheritance pattern. We performed genetic analysis of the proband using a targeted next generation sequencing (NGS) panel covering 17 known PD-causative genes. We identified a pathogenic missense mutation in VPS35 gene, c.1858G > A (p.D620N), in this patient.ConclusionsThis is the first report of the VPS35 p.D620N mutation in a Taiwanese family. Additionally, our report contributes to the current understanding of genetically defined PD patients treated successfully with STN-DBS.

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Dystonia is a clinically and genetically heterogeneous movement disorder. However, genetic causes of dystonia remain largely unknown in Asian subjects. To address this, we applied an integrated two-step approach that included gene dosage analysis and a next-generation sequencing panel containing 72 known genes causative for dystonia and related movement disorders to 318 Taiwanese patients with isolated or combined dystonia. Whole-genome sequencing was performed for one multiplex family with no known causative variant. The panel confirmed the genetic diagnosis in 40 probands (12.6%). We observed that a genetic diagnosis was more likely with juvenile onset compared with adult onset (24.2% vs 10.8%; P Z 0.03) and those with combined features, especially with myoclonus, compared with isolated dystonia (35.3% vs 10.5%; P Q4 Z 0.004). The most common causative genes were SGCE followed by GCH1, TH, CACNA1B, PRRT2, MR1, CIZ1, PLA2G6, and PRKN. Genetic causes were identified from single cases in TOR1A, TUBB4A, THAP1, ATP1A3, ANO3, GNAL, KMT2B, SLC6A3, ADCY5, CYP27A1, PANK2, C19orf12, and SPG11. The whole-genome sequencing analysis identified a novel intragenic deletion in OPHN1 in a multiplex family with X-linked dystonia and intellectual delay. Our findings delineate the genetic architecture and clinical spectrum of dystonia-causative pathogenic variants in an Asian population.

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Parkinson's disease (PD) is an incapacitating neurodegenerative disease. Patients with PD and their caregivers may have interactive effects on each other’s psychological well-being. This study aimed to assess the dyadic dynamics of resilience, fatigue, and suicidal ideation on the depression severity of PD patients and their caregivers. In total, 175 PD patients and 175 caregivers were recruited at a medical center from August 2018 to May 2020. Structural equation modeling (SEM) was used to examine the actor/partner effects on the psychological well-being of both the PD patients and their caregivers. The most common psychiatric diagnoses of both the PD patients (28.6%) and their caregivers (11.4%) were depressive disorders. The PD patients’ and their caregivers’ fatigue, suicidal ideation, and lack of resilience were significantly associated with the severity of their depression, respectively. Interactive effects existed between psychological well-being of individuals with PD and their caregivers. Clinicians must be aware of, and manage, these contributing factors between PD patients and their caregivers in order to prevent them from worsening each other’s depression.