Unique clinical and electrophysiological features in the peripheral nerve system in patients with sialidosis - a case series study.

BACKGROUND: To investigate the peripheral nervous system involvement in S sialidosis with typical features of myoclonus, seizure, and giant waves in somatosensory evoked potentials suggesting hyperexcitability in the central nervous system. METHODS: The clinical presentation of patients with genetically confirmed sialidosis was recorded. Neurophysiological studies, including nerve conduction studies (NCSs), F-wave studies, and needle electromyography (EMG), were performed on these patients. RESULTS: Six patients (M/F: 2:4) were recruited. In addition to the classical presentation, intermittent painful paresthesia was noted in four patients, and three of whom reported it as the earliest symptom. In the NCSs, one patient had reduced compound muscle action potential amplitudes in the right ulnar nerve, while another patient had prolonged distal motor latency in the bilateral tibial and peroneal nerves. Prolonged F-wave latency (83.3%), repeater F-waves (50%), and neurogenic polyphasic waves in EMG (in 2 out of 3 examined patients) were also noted. Interestingly, a very late response was noted in the F-wave study of all patients, probably indicating lesions involving the proximal peripheral nerve or spinal cord. CONCLUSION: In addition to the central nervous system, the peripheral nervous system is also involved in sialidosis, with corresponding clinical symptoms. Further study on these phenomena is indicated.

The role of the tongue in post-stroke dysphagia and obstructive sleep apnea: Correlation with sonography measurement.

OBJECTIVE: Obstructive sleep apnea (OSA) is a common risk factor for stroke, and dysphagia and pneumonia are both well-known complications of stroke. The development of these conditions is related to the oropharyngeal structures. We investigated whether specific structural features of the tongue may lead to the development of these complications. METHODS: Patients with ischemic stroke who required admission and community-dwelling elderly controls were enrolled. The participants underwent tongue measurements by received hand-held ultrasound, and received questionnaires to evaluate sleep quality and daytime sleepiness. The patient group also underwent objective sleep measurement by actigraphy and the 3-Step Swallowing Test (3-SSS). Sleep parameters and outcomes were analyzed. RESULTS: Patient with ischemic stroke had significantly thicker tongue than controls (6.53 cm v. 6.05 cm, p = 0.002). Multiple logistic regression analysis revealed that the anatomical parameters of the tongue in patients with stroke were significantly correlated with parameters of OSA, and the thickness of the tongue was positively correlated with the development of OSA (p = 0.024) and pneumonia (p = 0.048). CONCLUSIONS: A thicker-than average tongue may be a risk factor for OSA and pneumonia in patient with stroke. Hand-held ultrasound can be used to identify these anatomical features. Further studies are warranted to clarify the role of the tongue in these post-stroke complications.

Identification of an 85-kb Heterozygous 4p Microdeletion With Full Genome Analysis in Autosomal Dominant Charcot-Marie-Tooth Disease.

Background and Objectives: Charcot-Marie-Tooth disease (CMT) is a syndrome of a hereditary neurodegenerative condition affecting the peripheral nervous system and is a single gene disorder. Deep phenotyping coupled with advanced genetic techniques is critical in discovering new genetic defects of rare genetic disorders such as CMT. Methods: We applied multidisciplinary investigations to examine the neurophysiology and nerve pathology in a family that fulfilled the diagnosis of CMT2. When phenotype-guided first-tier genetic tests and whole-exome sequencing did not yield a molecular diagnosis, we conducted full genome analysis by examining phased whole-genome sequencing and whole-genome optical mapping data to search for the causal variation. We then performed a systematic review to compare the reported patients with interstitial microdeletion in the short arm of chromosome 4. Results: In this family with CMT2, we reported the discovery of a heterozygous 85-kb microdeletion in the short arm of chromosome 4 (4p16.3)[NC_000004.12:g.1733926_1819031del] spanning 3 genes [TACC3 (intron 6-exon 16), FGFR3 (total deletion), and LETM1 (intron 10-exon14)] that cosegregated with disease phenotypes in family members. The clinical features of peripheral nerve degeneration in our family are distinct from the well-known 4p microdeletion syndrome of Wolf-Hirschhorn syndrome, in which brain involvement is the major phenotype. Discussion: In summary, we used the full genome analysis approach to discover a new microdeletion in a family with CMT2. The deleted segment contains 3 genes (TACC3, FGFR3, and LETM1) that likely play a role in the pathogenesis of nerve degeneration.

Brain imaging signatures in amyotrophic lateral sclerosis: Correlation with peripheral motor degeneration.

OBJECTIVE: This study aimed to explore the clinical significance of brain imaging signatures in the context of clinical neurological deficits in association with upper and lower motor neuron degeneration in amyotrophic lateral sclerosis (ALS). METHODS: We performed brain MRI examinations to quantitatively evaluate (1) gray matter volume and (2) white matter tract fractional anisotropy (FA), axial diffusivity (AD), radial diffusivity (RD), and mean diffusivity (MD). Image-derived indices were correlated with (1) global neurological deficits of MRC muscle strength sum score, revised amyotrophic lateral sclerosis functional rating scale (ALSFRS-R), and forced vital capacity (FVC), and (2) focal scores of University of Pennsylvania Upper motor neuron score (Penn score) and the summation of compound muscle action potential Z scores (CMAP Z sum score). RESULTS: There were 39 ALS patients and 32 control subjects matched for age and gender. Compared to controls, ALS patients had a lower gray matter volume in the precentral gyrus of the primary motor cortex, which was correlated with FA of corticofugal tracts. The gray matter volume of the precentral gyrus was correlated with FVC, MRC sum score, and CMAP Z sum score, while the FA of the corticospinal tract was linearly associated with CMAP Z sum score and Penn score on multivariate linear regression model. INTERPRETATION: This study indicated that clinical assessment of muscle strength and routine measurements on nerve conduction studies provided surrogate markers of brain structural changes for ALS. Furthermore, these findings suggested parallel involvement of both upper and lower motor neurons in ALS.

Development of the Houston-Apollo model for older people living in remote areas in Taiwan.

AIM: Senior healthcare is challenging in remote areas, particularly in an economically disadvantaged population. This study examined the benefits of a combined healthcare system (Houston-Apollo model) in improvements of physical performance and medical care utilization of local older people. METHODS: People aged ≥65 years who participated in congregate meal services were recruited. Using concepts of telemedicine and community health records, participants received consultation from local general physicians, who provided advice or arranged referrals to the National Taiwan University Hospital Yunlin Branch. Physical parameters including blood pressure, body mass index, grip strength, walking speed, and five times sit-to-stand test (FTSST) were transferred to the National Taiwan University Hospital Yunlin Branch and local doctors in a timely manner. Changes in physical parameters and utilization of healthcare facilities were measured at the beginning of recruitment and 1 year later. RESULTS: In the 470 registered participants, 66% had hypertension, 50% had weakness in grip strength, 58% were slow at FTSST and 78% had disability in 6-meter walking speed. In total, 97 participants were followed up at 1 year. The systolic and diastolic blood pressure (mmHg) decreased from 137.4 to 133.3 (P = 0.019) and from 76.9 to 74.4 (P = 0.008), respectively. The time of FTSST (s) decreased from 11.3 to 10.4 (P = 0.011). The walking speed (m/s) increased from 0.71 to 0.74 (P = 0.039). Medical and dental outpatient usage increased by 2 and 1.14 times, respectively. CONCLUSIONS: The Houston-Apollo model could provide benefits for the physical status of older adults, promote proactive and preventive healthcare utilization, and contribute to medical equality. Geriatr Gerontol Int 2021; ••: ••-••.

A systematic review of late-onset and very-late-onset multiple acyl-coenzyme A dehydrogenase deficiency: Cohort analysis and patient report from Taiwan.

Multiple acyl-coenzyme A dehydrogenase deficiency (MADD) is a rare metabolic disorder with a dramatic clinical presentation. It was recently discovered that MADD may present at an advanced age. The clinical and laboratory data of an index patient and patients previously diagnosed at our institution were collected. A systematic review of previous studies retrieved from the PubMed, MEDLINE, and Embase databases published by February 1, 2020 was performed to collect patients with very-late-onset MADD (VLO-MADD, onset age > 60 years) globally and patients with late-onset MADD (LO-MADD, onset age < 60 years) in Taiwan. The clinical characteristics of the VLO-MADD patients were compared to those of LO-MADD patients. We report a patient with VLO-MADD who developed the first symptom at the age of 61 years. The patient presented with a Reye-like syndrome after taking aspirin for coronary artery disease. Repeated bouts of weakness were noted. Two variants of c.250 G > A (;) 419C > T were observed in the ETFDH gene. Another four patients with VLO-MADD were identified globally. Eighteen patients with LO-MADD were collected from our department and previously reported patients in Taiwan. There was no difference in the clinical symptoms (except for the onset age) or laboratory data between these two groups. Homozygous variants were not observed in any patients in the VLO-MADD group but were detected in 12 patients (66.6%) in the LO-MADD group (p = 0.014). Patients with MADD may first show symptoms in their 6th decade or beyond. The disease course may lead to erroneous diagnoses in this age group.

Early changes of nerve integrity in preclinical carriers of hereditary transthyretin Ala117Ser amyloidosis with polyneuropathy.

BACKGROUND AND PURPOSE: Disease-modifying therapies provide new horizons for hereditary transthyretin amyloidosis with polyneuropathy (ATTRv-PN) to slow neuropathic progression. Initiating treatment at the earliest time requires biomarkers reflecting both small- and large-fiber degeneration in carriers. METHODS: This study included examinations of pathology (intraepidermal nerve fiber [IENF] density), physiology (nerve conduction studies, autonomic function test, and nerve excitability), and psychophysics (thermal thresholds) in carriers to compare to healthy controls and asymptomatic diabetic patients. RESULTS: There were 43 carriers (44.2 ± 11.4 years, p.Ala117Ser in 42 carriers), 43 controls (43.4 ± 12.7 years) including 26 noncarrier families, and 50 asymptomatic diabetic patients (58.1 ± 9.5 years). Carriers had lower IENF densities than controls and similar densities as diabetic patients. Median nerve conduction parameters, especially distal motor latency, were the most frequent neurophysiological abnormality in carriers, could differentiate carriers from controls and diabetic patients, were correlated with IENF densities in carriers but not in controls and diabetic patients, and were correlated with nerve excitability parameters in carriers but not in controls. Fifteen carriers (34.9%) with electrophysiological evidence of median nerve entrapment at the wrist had lower IENF densities and more abnormal conduction parameters than carriers without. We defined nerve dysfunction index-the ratio of median distal motor latency to IENF density-which differentiated carriers from controls. CONCLUSIONS: In late-onset ATTRv-PN carriers with predominant p.Ala117Ser, median conduction parameters were the most common neurophysiological abnormalities and served as surrogate signatures of small- and large-fiber impairment. Combination of median distal motor latency and IENF density can reflect early neuropathy in carriers.

Early recurrence of ischemic stroke in patients receiving endovascular thrombectomy.

BACKGROUND/PURPOSE: Endovascular thrombectomy (EVT) is effective in treating acute ischemic stroke associated with large vessel occlusion. Early recurrence of ischemic stroke (ERIS) after EVT, however, is a devastating event and could worsen the condition of patient. Current study aimed to investigate the prevalence and risk factors of ERIS after EVT. METHODS: The medical records of all patients receiving EVT at a single medical center were reviewed and analyzed. ERIS was defined as presentation of newly developed neurological deficits in previously recanalized vascular territory or another vascular territory that was not initially involved within 30 days of the index stroke. RESULTS: From January 2015 to September 2018, a total of 200 patients (71.6 ± 12.3 years, male 49%) had received EVT and 17 patients (8.5%) developed ERIS. Presence of valvular heart disease was the only clinical factor associated with ERIS (OR: 4.26, 95% CI: 1.16-17.7). Patients with ERIS had significantly worse modified Rankin scale at 3 months (common OR: 3.11, 95% CI: 1.18-8.73) and were independently associated with mortality (OR: 7.73, 95% CI: 2.00-30.6). Ten of 17 patients with ERIS had received repeated EVT and all achieved good recanalization without procedure-related complications or symptomatic intracerebral hemorrhage. CONCLUSION: ERIS in patients receiving EVT was not rare, especially in those with valvular heart disease, and was associated with worse outcome. Nevertheless, they could be safely treated by repeated EVT.

A limb-girdle myopathy phenotype of RUNX2 mutation in a patient with cleidocranial dysplasia: a case study and literature review.

BACKGROUND: Cleidocranial dysplasia (CCD) is a rare hereditary disorder that arises from heterozygous loss of function mutations in the runt-related transcription factor 2 (RUNX2) gene. As RUNX2 is mainly expressed in osteoblasts, CCD typically affects the skeletal and dental systems. Few studies have investigated RUNX2 mutation effects on non-skeletal systems. Here, we describe limb-girdle myopathy, an uncommon phenotype of CCD, in a patient with a heterozygous missense mutation (p.R225Q) in the RUNX2 gene. CASE PRESENTATION: A 58 year-old man presented with progressive back pain and six months of weakness in the proximal parts of all four limbs. Physical examinations showed that he was short in stature (height, 164.4 cm; weight, 79.1 kg) with a dysmorphic face, including hypertelorism, midface hypoplasia, and chin protrusion. At a young age, he had received orthodontic surgery, due to dental abnormalities. Neurological examinations revealed sloping shoulders, weakness, and atrophy in the proximal areas of the arms, shoulder girdle muscles, and legs. The deep tendon reflex and sensory system were normal. Radiological examinations revealed mild scoliosis, shortened clavicles, and a depressed skull bone, which were consistent with a clinical diagnosis of CCD. Electromyography (EMG) studies showed myogenic polyphasic waves in the deltoid, biceps brachii, and rectus femoris muscles. Instead, the EMG findings were normal in the first dorsal interosseous, tibialis anterior and facial muscles. The EMG findings were compatible with a limb-girdle pattern with facial sparing. The patient's family history showed his father and eldest daughter with similar dysmorphic faces, skeletal disorders and proximal upper extremity weakness. We sequenced the RUNX2 gene and discovered a heterozygous missense mutation (c.G674A, p.R225Q), which altered the C-terminal end of the RUNX2 protein. This mutation was predicted to inactivate the protein and might affect its interactions with other proteins. This mutation co-segregated with the disease phenotypes in the family. CONCLUSIONS: We described limb-girdle myopathy in a patient with CCD that carried a heterozygous RUNX2 missense mutation. This uncommon phenotype expanded the phenotypic spectrum of the RUNX2 p.R225Q mutation. The role of RUNX2 in myogenic development merits future studies. Our findings remind clinicians that myopathic patients with myopathies combined with facial dysmorphism and shortened clavicles should consider the diagnosis of CCD.