Anti-SRP Myopathy with Sensorimotor Polyneuropathy: A Case Report.

PURPOSE: Anti-signal recognition particle (SRP) myopathy is a subtype of immune-mediated necrotizing myopathy. It rarely presents with extramuscular features, involving the skin, lung, and heart. This paper presents a case of anti-SRP myopathy associated with sensorimotor polyneuropathy. CASE REPORT: A 33-year-old woman with no history of systemic disease presented to our hospital with weakness and numbness of the lower limbs for 1 year. Electromyography and nerve conduction study (NCS) revealed combined myopathy and axonal sensorimotor polyneuropathy. Blood examination revealed increased levels of serum muscle enzymes and anti-SRP antibodies. T1-weighted magnetic resonance imaging revealed diffuse muscular hyperintensities in the thighs, indicative of fatty replacement. She was administered methylprednisolone pulse therapy, followed by oral prednisolone and azathioprine. Muscle power increased, and serum muscle enzyme levels decreased significantly. Subsequent NCS performed 2 years later revealed persistent axonal degeneration in the lower limbs. CONCLUSION: Anti-SRP myopathy can present with sensorimotor polyneuropathy. Thus, the possibility that the same pathological process affected the skeletal muscles and peripheral nerves should be considered.

Cranial nerve Palsy following COVID-19 Vaccination Responsive to Plasma Exchange.

BACKGROUND: Globally, mass COVID-19 vaccine administration has revealed various adverse effects of the vaccine, such as various neurological symptoms, which are currently identified as a result of an excessive immune response. CASE REPORT: A 70-year-old woman presented with progressive unilateral oculomotor nerve palsy and decreased visual acuity 12 days after receiving the Moderna COVID-19 vaccine. In adults, such palsy is typically caused by microvascular disease (ischemia) or compressive tumors. Given the temporal relationship between vaccination and symptoms and the exclusion of other possible causative factors, the patient's oculomotor nerve palsy and optic nerve involvement was considered to be related to the vaccination. Cranial nerve palsy following COVID-19 vaccination was diagnosed, and after pulse steroid and plasma exchange, the patient showed steady recovery. CONCLUSION: Our patient with cranial nerve palsy following COVID-19 vaccination responded well to plasma exchange after limited improved toward steroid. This case highlights the importance of early identification and treatment of the immunological effects of COVID-19 vaccines on cranial nerves.

Phenotypic Heterogeneity in Patients with Mutations in the Mitochondrial Complex I Assembly Gene NDUFAF5.

BACKGROUND: Rare mutations in NADH:ubiquinone oxidoreductase complex assembly factor 5 (NDUFAF5) are linked to Leigh syndrome. OBJECTIVE: We aimed to describe clinical characteristics and functional findings in a patient cohort with NDUFAF5 mutations. METHODS: Patients with biallelic NDUFAF5 mutations were recruited from multi-centers in Taiwan. Clinical, laboratory, radiological, and follow-up features were recorded and mitochondrial assays were performed in patients' skin fibroblasts. RESULTS: Nine patients from seven unrelated pedigrees were enrolled, eight homozygous for c.836 T > G (p.Met279Arg) in NDUFAF5 and one compound heterozygous for p.Met279Arg. Onset age had a bimodal distribution. The early-onset group (age <3 years) presented with psychomotor delay, seizure, respiratory failure, and hyponatremia. The late-onset group (age ≥5 years) presented with normal development, but slowly progressive dystonia. Combing 25 previously described patients, the p.Met279Arg variant was exclusively identified in Chinese ancestry. Compared with other groups, patients with late-onset homozygous p.Met279Arg were older at onset (P = 0.008), had less developmental delay (P = 0.01), less hyponatremia (P = 0.01), and better prognosis with preserved ambulatory function into early adulthood (P = 0.01). Bilateral basal ganglia necrosis was a common radiological feature, but brainstem and spinal cord involvement was more common with early-onset patients (P = 0.02). A modifier gene analysis showed higher concomitant mutation burden in early-versus late-onset p.Met279Arg homozygous cases (P = 0.04), consistent with more impaired mitochondrial function in fibroblasts from an early-onset case than a late-onset patient. CONCLUSIONS: The p.Met279Arg variant is a common mutation in our population with phenotypic heterogeneity and divergent prognosis based on age at onset. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Case Report: Severe rebound after withdrawal of fingolimod in a patient with neuromyelitis optica spectrum disorder.

Purpose: Fingolimod, an oral treatment for relapsing-remitting multiple sclerosis (RRMS), has been associated with a significant rebound in disease activity after therapy cessation. We described a patient with neuromyelitis optica spectrum disorder (NMOSD) who was previously diagnosed with RRMS and experienced fatal rebound syndrome after cessation of fingolimod. Case report: A 54-year-old woman, previously diagnosed with RRMS, experienced relapse after orthopedic surgery. The diagnosis was later revised to NMOSD based on a positive aquaporin-4 antibody. Three weeks after converting the immunomodulator from fingolimod to azathioprine, severe disease reactivation was observed. Considering the multiple new and enlarging magnetic resonance imaging lesions, the temporal relationship between fingolimod cessation and symptom onset, and the relatively low possibility of disease reactivation within a short time, the diagnosis of fingolimod withdrawal syndrome was proposed. Although immediate steroid pulse therapy and plasma exchange were performed, the patient eventually died owing to a fulminant clinical course. Conclusion: Fingolimod withdrawal syndrome is well known in patients with multiple sclerosis (MS). It can also occur in patients with NMOSD. Recognizing patients with NMOSD who present with MS-like manifestations, and avoiding drugs that may be harmful to patients with NMOSD, are important.

Risk of Migraine after Traumatic Brain Injury and Effects of Injury Management Levels and Treatment Modalities: A Nationwide Population-Based Cohort Study in Taiwan.

Traumatic brain injury (TBI) causes several long-term disabilities, particularly headaches. An association between TBI and subsequent migraine has been reported. However, few longitudinal studies have explained the link between migraine and TBI. Moreover, the modifying effects of treatment remain unknown. This retrospective cohort study used records from Taiwan's Longitudinal Health Insurance Database 2005 to evaluate the risk of migraine among patients with TBI and to determine the effects of different treatment modalities. Initially, 187,906 patients, aged ≥ 18 years, who were diagnosed as TBI in 2000, were identified. In total, 151,098 patients with TBI and 604,394 patients without TBI were matched at a 1:4 ratio according to baseline variables during the same observation period. At the end of follow-up, 541 (0.36%) and 1491 (0.23%) patients in the TBI and non-TBI groups, respectively, developed migraine. The TBI group exhibited a higher risk of migraine than the non-TBI group (adjusted HR: 1.484). Major trauma (Injury Severity Score, ISS ≥ 16) was associated with a higher migraine risk than minor trauma (ISS < 16) (adjusted HR: 1.670). However, migraine risk did not differ significantly after surgery or occupational/physical therapy. These findings highlight the importance of long-term follow-up after TBI onset and the need to investigate the underlying pathophysiological link between TBI and subsequent migraine.

Case report: Hemophagocytic lymphohistiocytosis complicated by multiple organ dysfunction syndrome following aseptic encephalitis.

Hemophagocytic lymphohistiocytosis (HLH) is a rare but potentially life-threatening condition caused by excessive immune activation. Secondary HLH is usually triggered by infection, most often from viral infection or malignancy. Here, we present a case of secondary HLH, complicated by multiple organ dysfunction syndrome triggered by critical aseptic encephalitis. A 27-year-old man without any underlying disease presented to our hospital with fever, disturbance of consciousness, and generalized seizures. The patient was diagnosed with aseptic encephalitis with super-refractory status epilepticus. Although antiseizure medications and immunoglobulins were administered, the patient developed multiple organ dysfunction syndrome. HLH was later diagnosed based on hypertriglyceridemia, hyperferritinemia, splenomegaly, cytopenia, and phagocytosis of nucleated cells, as shown by a blood smear of bone marrow aspiration. Treatment with pulse steroid therapy and plasmapheresis was initiated rather than chemotherapy because of the patient's critical condition. However, the patient died of profound shock and multiple organ failure. Diagnosis of HLH is challenging in patients with severe infections because of similar clinical manifestations and laboratory findings. The early recognition of HLH provides patients with the opportunity to receive appropriate treatment, which can lead to increased survival and remission rates.

The optimal pulse pressures for healthy adults with different ages and sexes correlate with cardiovascular health metrics.

Background: Pulse pressure (PP) may play a role in the development of cardiovascular disease, and the optimal PP for different ages and sexes is unknown. In a prospective cohort, we studied subjects with favorable cardiovascular health (CVH), proposed the mean PP as the optimal PP values, and demonstrated its relationship with healthy lifestyles. Methods and results: Between 1996 and 2016, a total of 162,636 participants (aged 20 years or above; mean age 34.9 years; 26.4% male subjects; meeting criteria for favorable health) were recruited for a medical examination program. PP in male subjects was 45.6 ± 9.4 mmHg and increased after the age of 50 years. PP in female subjects was 41.8 ± 9.5 mmHg and increased after the age of 40 years, exceeding that of male subjects after the age of 50 years. Except for female subjects with a PP of 40-70 mmHg, PP increase correlates with both systolic blood pressure (BP) increase and diastolic BP decrease. Individuals with mean PP values are more likely to meet health metrics, including body mass index (BMI) <25 kg/m2 (chi-squared = 9.35, p<0.01 in male subjects; chi-squared = 208.79, p < 0.001 in female subjects) and BP <120/80 mmHg (chi-squared =1,300, p < 0.001 in male subjects; chi-squared =11,000, p < 0.001 in female subjects). We propose a health score (Hscore) based on the sum of five metrics (BP, BMI, being physically active, non-smoking, and healthy diet), which significantly correlates with the optimal PP. Conclusion: The mean PP (within ±1 standard deviation) could be proposed as the optimal PP in the adult population with favorable CVH. The relationship between health metrics and the optimal PP based on age and sex was further demonstrated to validate the Hscore.

Use of Hormone Replacement Therapy and Risk of Dementia: A Nationwide Cohort Study.

OBJECTIVE: Estrogen has the potential to influence brain physiology implicated in dementia pathogenesis. Hormone replacement therapy (HRT) might be expected to influence the risk of dementia. Observational data indicated that HRT was associated with reductions in dementia risk, but experimental evidence demonstrates that HRT increases the incidence of dementia. To determine the effect of HRT on risk of dementia, a retrospective cohort study was performed using a nationwide claims dataset in Taiwan. METHODS: A population-base longitudinal study was performed using data from the Longitudinal Health Insurance Database in Taiwan. A total of 35,024 women with HRT were enrolled as the exposed cohort and 70,048 women without HRT were selected on the basis of propensity matching as the comparison cohort. All of the subjects were followed up until the diagnosis of dementia, death, or at the end of December 31, 2013, whichever occurred first. Overall, the average duration of follow-up (±SD) in the HT and comparison cohort was 12.3(±2.3) and 12.2 (±2.4), respectively. The Cox proportional hazards regression models were conducted to produce hazard ratios (HRs) with 95% confidence intervals (CIs) to evaluate the association of HRT with the risk of dementia. RESULTS: In the follow-up period, the cumulative incidence of dementia for the HRT cohort (20.04 per 1,000) was significantly higher than the corresponding cumulative incidence for the comparison cohort (15.79 per 1,000), resulting in an adjusted hazard ratio of 1.35 (95% CI, 1.13-2.62). There was an increased risk of dementia with a higher cumulative dose of HRT prescription (p for trend <0.0001). CONCLUSION: This cohort study documented that HRT was associated with an increased risk of dementia. The clinical implications of this study merit further investigations.

Case report: Vaccine-induced immune thrombotic thrombocytopenia complicated by acute cerebral venous thrombosis and hemorrhage after AstraZeneca vaccines followed by Moderna COVID-19 vaccine booster and surgery.

Vaccine-induced thrombotic thrombocytopenia (VITT) is a well-known complication of adenoviral vector COVID-19 vaccines including ChAdOx1 nCoV-19 (AstraZeneca) and Ad26. COV2.S (Janssen, Johnson & Johnson). To date, only a few cases of mRNA COVID-19 vaccine such as mRNA-1273 (Moderna) or BNT162b2 (Pfizer-BioNTech)-induced VITT have been reported. We report a case of VITT with acute cerebral venous thrombosis and hemorrhage after a booster of mRNA-1273 (Moderna) vaccine in a patient previously vaccinated with two doses of the AstraZeneca vaccine. A 42-year-old woman presented with sudden onset of weakness of the right upper limb with focal seizure. She had received two doses of AstraZeneca vaccines and a booster with Moderna vaccine 32 days before presentation. She had also undergone a laparoscopic myomectomy 12 days previously. Laboratory examinations revealed anemia (9.5 g/dl), thrombocytopenia (31 × 103/µl), and markedly elevated d-dimer (>20.0 mg/L; reference value < 0.5 mg/L). The initial brain computed tomography (CT) was normal, but a repeated scan 10 h later revealed hemorrhage at the left cerebrum. Before the results of the blood smear were received, on suspicion of thrombotic microangiopathy with thrombocytopenia and thrombosis, plasmapheresis and pulse steroid therapy were initiated, followed by intravenous immunoglobulin (1 g/kg/day for two consecutive days) due to refractory thrombocytopenia. VITT was confirmed by positive anti-PF4 antibody and both heparin-induced and PF4-induced platelet activation testing. Clinicians should be aware that mRNA-1273 Moderna, an mRNA-based vaccine, may be associated with VITT with catastrophic complications. Additionally, prior exposure to the AstraZeneca vaccine and surgical procedure could also have precipitated or aggravated autoimmune heparin-induced thrombocytopenia/VITT-like presentation.

Increased risk of sleep-related movement disorder in patients with Helicobacter pylori infection: A nationwide population-based study.

Background and purpose: Evidence increasingly suggests that Helicobacter pylori infection (HPI) is associated with movement disorders such as Parkinson's disease (PD). However, the relationship between HPI and sleep-related movement disorders (SRMD) remains unknown. This nationwide population-based study tried to demonstrate whether patients with HPI have a higher risk of developing SRMD in a general adult population. Methods: The study cohort enrolled 9,393 patients who were initially diagnosed with HPI between 2000 and 2013. Notably, 37,572 age- and sex-matched controls without prior HPI were selected as the reference. A Cox proportional hazard regression analysis was performed for multivariate adjustment. Results: Patients with HPI had a higher risk of developing SRMD (adjusted hazard ratio [HR] = 2.18, 95% confidence interval [CI] = 1.26-3.82, p < 0.01). Patients with HPI aged ≥65 years exhibited the highest risk (HR = 3.01, 95% CI = 1.90-5.30, p < 0.001), followed by patients aged 45-64 years (HR = 1.69, 95% CI = 1.26-2.90, p <0.01) and <45 years (HR = 1.49, 95% CI = 1.12-2.49, p < 0.01). Patients were most likely to develop SRMD 5 years or more after diagnosis of HPI (HR = 3.33, 95% CI = 1.97-5.89, p < 0.001). The increased risk of SRMD in male patients with HPI (HR = 2.73, 95% CI = 1.53-4.79, p < 0.001) was greater than in female patients (HR = 1.14, 95% CI = 1.04-1.65, p < 0.05). Conclusion: Patients with HPI were associated with an increased risk for SRMD, with a higher risk in men, aged ≥65 years, and diagnosed for more than 5 years.

Clinical and genetic characterization of a Taiwanese cohort with spastic paraparesis combined with cerebellar involvement.

Hereditary spastic paraplegias (HSPs) are a heterogeneous group of neurodegenerative disorders clinically characterized by progressive lower-limb spasticity. Cerebellar ataxia commonly co-occurs with complicated HSPs. HSP with concurrent cerebellar ataxia has significant clinical and genetic overlaps with hereditary cerebellar ataxia (HCA) and other inherited neurological diseases, adding to the challenge of planning genetic testing for the disease. In this study, we characterized clinical features of a cohort of 24 patients (male/female: 15/9) from 22 families who presented spastic paraparesis combined with cerebellar involvement, with a median disease onset age 20.5 (range 5-53) years. Aside from the core phenotype, 18 (75%) patients had additional neuropsychiatric and systemic manifestations. A stepwise genetic testing strategy stratified by mode of inheritance, distinct neuroimaging features (e.g., thin corpus callosum), population-specific prevalence and whole-exome sequencing was utilized to investigate the genetic etiology. Causative mutations in up to 10 genes traditionally related to HSP, HCA and other neurogenetic diseases (autosomal recessive spastic ataxia of Charlevoix-Saguenay, neurodegeneration with brain iron accumulation, and progressive encephalopathy with brain atrophy and thin corpus callosum) were detected in 16 (73%) of the 22 pedigrees. Our study revealed the genetic complexity of HSP combined with cerebellar involvement. In contrast to the marked genetic diversity, the functions of the causative genes are restricted to a limited number of physiological themes. The functional overlap might reflect common underlying pathogenic mechanisms, to which the corticospinal tract and cerebellar neuron circuits may be especially vulnerable.

A Metallomic Approach to Assess Associations of Plasma Metal Levels with Amnestic Mild Cognitive Impairment and Alzheimer's Disease: An Exploratory Study.

Alzheimer's disease (AD) involves the abnormal activity of transition metals and metal ion dyshomeostasis; however, the potential of trace metal biomarkers in predicting cognitive decline has not been evaluated. This study aimed to assess the potential of 36 trace elements in predicting cognitive decline in patients with amnestic mild cognitive impairment (aMCI) or AD. Participants (9 controls, 23 aMCI due to AD, and 8 AD dementia) underwent comprehensive cognitive tests, including the Mini-Mental State Examination (MMSE) and trace metal analysis. The correlations between the plasma trace element levels and annual MMSE changes during follow-up were analyzed. We found that an increase in disease severity was linked to lower plasma levels of boron (B), bismuth (Bi), thorium (Th), and uranium (U) (adjusted p < 0.05). Higher baseline calcium levels (r = 0.50, p = 0.026) were associated with less annual cognitive decline; those of B (r = −0.70, p = 0.001), zirconium (r = −0.58, p = 0.007), and Th (r = −0.52, p = 0.020) with rapid annual cognitive decline in the aMCI group; and those of manganese (r = −0.91, p = 0.035) with rapid annual cognitive decline in the AD group. Overall, our exploratory study suggests that plasma metal levels have great potential as in vivo biomarkers for aMCI and AD. Larger sample studies are necessary to confirm these results.

Cystic Encephalomalacia in a Young Woman After Cardiac Arrest Due to Diabetic Ketoacidosis and Thyroid Storm.

Cystic encephalomalacia is commonly reported in neonates with prenatal or perinatal hypoxic events. It is rarely observed in adults. A 25-year-old woman with a history of type 1 diabetes mellitus and hyperthyroidism presented to the emergency department with diabetic ketoacidosis (DKA) and a thyroid storm. She sustained cardiac arrest due to ventricular fibrillation and subsequently developed hypoxic encephalopathy. Initial brain computed tomography showed no significant findings; however, follow-up magnetic resonance imaging three months later revealed cystic encephalomalacia in the bilateral parieto-occipital lobes. A Tc-99m ethyl cysteinate dimer (ECD) brain perfusion scan revealed extensive hypoperfusion in the bilateral frontal and parieto-occipital lobes. She showed severe cognitive impairment and marked spasticity in all her limbs. Although cystic encephalomalacia is mostly reported in neonates with hypoxic injury, it can be seen in adults with hypoxic encephalopathy, leading to a significant neurological deficit.

Primary Familial Brain Calcification Caused by a Novel Compound Heterozygous Mutation in the MYORG Gene.

BACKGROUND PURPOSE: To demonstrate a novel compound heterozygous mutation in MYORG-related recessive primary familial brain calcification. CASE REPORT: We report a case of primary familial brain calcification with newly-discovered compound heterozygous mutation in the MYORG gene presenting with progressive parkinsonism, cerebellar signs, and typical diffuse brain calcifications. CONCLUSION: Clinicians should consider MYORG testing in patients who have primary brain calcifications with either a negative or recessive family history.

Optimal Scaling Approaches for Perfusion MRI with Distorted Arterial Input Function (AIF) in Patients with Ischemic Stroke.

BACKGROUND: Diagnosis and timely treatment of ischemic stroke depends on the fast and accurate quantification of perfusion parameters. Arterial input function (AIF) describes contrast agent concentration over time as it enters the brain through the brain feeding artery. AIF is the central quantity required to estimate perfusion parameters. Inaccurate and distorted AIF, due to partial volume effects (PVE), would lead to inaccurate quantification of perfusion parameters. METHODS: Fifteen patients suffering from stroke underwent perfusion MRI imaging at the Tri-Service General Hospital, Taipei. Various degrees of the PVE were induced on the AIF and subsequently corrected using rescaling methods. RESULTS: Rescaled AIFs match the exact reference AIF curve either at peak height or at tail. Inaccurate estimation of CBF values estimated from non-rescaled AIFs increase with increasing PVE. Rescaling of the AIF using all three approaches resulted in reduced deviation of CBF values from the reference CBF values. In most cases, CBF map generated by rescaled AIF approaches show increased CBF and Tmax values on the slices in the left and right hemispheres. CONCLUSION: Rescaling AIF by VOF approach seems to be a robust and adaptable approach for correction of the PVE-affected multivoxel AIF. Utilizing an AIF scaling approach leads to more reasonable absolute perfusion parameter values, represented by the increased mean CBF/Tmax values and CBF/Tmax images.

Sudden onset hearing loss as initial presentation of Susac syndrome: a rare case report and brief review.

Susac syndrome is a rare disease presenting with a classic triad of symptoms. These are sensorineural hearing loss, encephalopathy, and branch retinal artery occlusions. Initial presentation is usually headache and symptoms of encephalopathy. Hearing loss is unusual in the early stages but, when it does present, can often lead to a misdiagnosis of sudden sensorineural hearing loss. Hence, neurological and retinal examinations are essential to an accurate diagnosis. In this study, we aimed to raise awareness of Susac syndrome among physicians and facilitate recognition of its manifestation, especially in those patients presenting with hearing loss alone. Identifying Susac syndrome that presents as sudden sensorineural hearing loss can be challenging but a number of case reviews have been reported in recent years and treatment guidelines are available.

Steroid-Responsive Gradenigo's Syndrome Mimicking Subdural Hematoma.

Gradenigo's syndrome (GS) is featured by a clinical triad of otorrhea, retro-orbital pain, and a sixth nerve palsy. Clinical examination is crucial prior to considering neuroimaging. The majority of cases are secondary to infection thus requiring long-term broad-spectrum antibiotics; severe cases also require surgical intervention for risk of intracranial abscess or even death. The patient was a 35-year-old female who presented with right temporal headache and right retro-orbital pain. The initial diagnosis from the local clinic was of subdural hemorrhage. Cranial nerve (CN) VI paresis was noted upon examination and inflammatory process was documented based on brain MR. The patient was diagnosed with Gradenigo's syndrome and administered antibiotics and steroids. Symptoms recurred after cessation of steroids and once antibiotics-related fever developed. The symptoms resolved after stopping the antibiotics and reintroducing steroids. The MRI performed after three months recorded no brain inflammation. We report a Gradenigo's syndrome caused by chronic inflammation with good response to steroids. To our best knowledge, there were merely approximately 80 patients who were reported with Gradnigo or Gradenigo's syndrome before. Infection comprised 76% of cases, thus broad-spectrum and long-term antibiotics use have been emphasized instead of steroid use. However, steroids also play an important role in reducing nerve injury by edematous change.

Treatable Rapid Progressive Dementia: A First Case Report of Anti-dipeptidyl-peptidase-like Protein 6 Encephalitis in Taiwan.

PURPOSE: Anti-dipeptidyl-peptidase-like protein 6 (DPPX) encephalitis is a rare but treatable autoimmune disorder, characterized by gastrointestinal symptoms, cognitive dysfunction, and central nervous system hyperexcitability. CASE REPORT: Herein, we report a case of an 80-year-old male patient who presented with unexplained diarrhea, weight loss, rapidly progressive dementia, tremors, and myoclonus. His serum tested positive for anti-DPPX antibodies. He was treated with plasma exchange, oral prednisolone, and azathioprine. All his symptoms improved substantially after treatment. CONCLUSION: Early recognition of anti-DPPX encephalitis is important because it can be treated with immunotherapy. To the best of our knowledge, this is the first reported case of anti-DPPX encephalitis in Taiwan.