Recurrent Bilateral Lower Motor Neuron Type of Facial Palsy with Hearing Impairment: Hyperphosphatemic Familial Tumoral Calcinosis

Hyperphosphatemic familial tumoral calcinosis (HFTC) presents with varied neurological manifestations that have been reported in the literature like facial palsy, vision and hearing impairment, stroke, and headache. In this article, we reported a 12-year-old girl child patient with recurrent facial weakness with bilateral hearing impairment and multiple ulcerative lesions on lower limbs and elbows. On examination, she had lower motor neuron (LMN) facial palsy with conductive hearing loss. The investigations showed hyperphosphatemia (9.3 mg/dL) with normal serum calcium (10.4 mg/dL), alkaline phosphatase (147.9 U/L), parathyroid hormone (23.12 pg/mL), and renal function tests. Elevated serum calcium and phosphorus product (96.72 mg2/mL2) and elevated renal tubular reabsorption of phosphate (TMPxGFR) value (9.16) were noted. Skeletal survey showed hyperostosis in the long bone diaphysis, vertebrae, ribs, pelvic bone, skull, and facial bones with narrowing of cranial ostium, characteristically without any peri-articular soft tissue calcifications. An angiogram showed multiple intravascular calcifications. She was managed with a low-phosphate diet, sevelamer, niacinamide, acetazolamide, sucroferric oxyhydroxide to lower serum phosphate level, and topical sodium thiosulfate ectopic cutaneous calcification. Exome sequencing showed novel homozygous inframe deletion of ACG in FGF23 gene exon 3 at c.374_376 delins position (p. Asp125del) in the proband and a mutation in the heterozygous state in the mother and elder sibling, thus confirming a molecular diagnosis of HFTC. Our case had a unique neurological presentation of recurrent bilateral lower motor nerve facial palsy, hearing loss, multiple ectopic cutaneous calcifications without peri-articular deposits, multiple intravascular, intracranial, and vertebral endplate calcification, which has not been reported earlier. The proband showed a novel pathogenic variant suggesting an expanding phenotype of HFTC.

Subacute Spinal Subdural Hematoma in One-Year Old Boy Due to Severe Hemophilia A

Background: Paraparesis may result from a variety of or primary central nervous system conditions or systemic disorders, and although rare, it may also caused by spinal cord hemorrhage. Spontaneous spinal subdural hematomas (SSDH) are most frequently associated with coagulopathies. People with congenital clotting disorders such as hemophilia are at increased risk for experiencing spontaneous spinal subdural hemorrhage at unusual sites, which is a rare case and a neurological emergency required urgent recognition. We report a boy with paraparesis caused by subacute SSDH due to hemophilia A. Case Presentation: A 15 month-old boy, with chief complain of difficulty in moving his leg and pain when walking, physical examination revealed a lower motor neuron lesion, laboratory showed a low factor VIII at 0.4% level, Magnetic Resonance Imaging (MRI) showed anterior and posterior displacement of the spinal cord due to the presence of the subacute subdural hematoma extending from 1st cervical to 1st lumbar spine. He assessed with inferior paraparesis caused by subacute spinal subdural hematoma due to hemophilia A. The patient’s condition was improved after received replacement therapy of factor VIII and proper laminectomy neurosurgery. Conclusion: This case showed an approach for a comprehensive diagnostic and management for a rare case of paraparesis due to hemophilia. Pay attention to the physical examination which shows a lower motor neuron lesion in an acute paralysis cases, there is still a possibility that it is an upper motor neuron lesion.

Rapid generation of ventral spinal cord-like astrocytes from human iPSCs for modeling non-cell autonomous mechanisms of lower motor neuron disease

Astrocytes play important roles in the function and survival of neuronal cells. Dysfunctions of astrocytes are associated with numerous disorders and diseases of the nervous system, including motor neuron diseases such as amyotrophic lateral sclerosis (ALS). Human induced pluripotent stem cell (iPSC)-based approaches are becoming increasingly important for the study of the mechanisms underlying the involvement of astrocytes in non-cell autonomous processes of motor neuron degeneration in ALS. These studies must account for the molecular and functional diversity among astrocytes in different regions of the brain and spinal cord. It is essential that the most pathologically-relevant astrocyte preparations are used when investigating non-cell autonomous mechanisms of either upper or lower motor neuron degeneration in ALS. In this context, the main aim of this study was to establish conditions enabling rapid and robust generation of physiologically-relevant ventral spinal cord-like astrocytes that would provide an enhanced experimental model for the study of lower motor neuron degeneration in ALS. Neural progenitor cells with validated caudal and ventral features were derived from human iPSCs and differentiated into astrocytes, which were then characterized by examining morphology, markers of ventral spinal cord astrocytes, spontaneous and induced calcium transients, and astrogliosis markers. Efficient and streamlined generation of human iPSC-derived astrocytes with molecular and biological properties similar to physiological astrocytes in the ventral spinal cord was achieved. These induced astrocytes express markers of mature ventral spinal cord astrocytes, exhibit spontaneous and ATP-induced calcium transients, and lack signs of overt activation. Human iPSC-derived astrocytes with ventral spinal features offer advantages over more generic astrocyte preparations for the study of both ventral spinal cord astrocyte biology and the involvement of astrocytes in mechanisms of lower motor neuron degeneration in ALS.

Juvenile Amyotrophic Lateral Sclerosis: A Review

Juvenile amyotrophic lateral sclerosis (JALS) is a rare group of motor neuron disorders with gene association in 40% of cases. JALS is defined as onset before age 25. We conducted a literature review of JALS and gene mutations associated with JALS. Results of the literature review show that the most common gene mutations associated with JALS are FUS, SETX, and ALS2. In familial cases, the gene mutations are mostly inherited in an autosomal recessive pattern and mutations in SETX are inherited in an autosomal dominant fashion. Disease prognosis varies from rapidly progressive to an indolent course. Distinct clinical features may emerge with specific gene mutations in addition to the clinical finding of combined upper and lower motor neuron degeneration. In conclusion, patients presenting with combined upper and lower motor neuron disorders before age 25 should be carefully examined for genetic mutations. Hereditary patterns and coexisting features may be useful in determining prognosis.

A Novel Variant in Superoxide Dismutase 1 Gene (p.V119M) in Als Patients with Pure Lower Motor Neuron Presentation

Amyotrophic lateral sclerosis (ALS) is a progressive and fatal disorder characterized by degeneration of motor neurons in the cerebral cortex, brain stem, and spinal cord. Most cases of ALS appear sporadically, but 5–10% of patients have a family history of disease. Mutations in the superoxide dismutase 1 gene (SOD1) have been found in 12–23% of familial cases and in 1–2% of sporadic cases. Currently, more than 180 different SOD1 gene variants have been identified in ALS patients. Here, we describe two apparently sporadic ALS patients carrying the same SOD1 c.355G>A variant, leading to the p.V119M substitution, not previously described. Both the patients showed pure lower motor neuron phenotype. The former presented with the flail leg syndrome, a rare ALS variant, characterized by progressive distal onset weakness and atrophy of lower limbs, slow progression and better survival than typical ALS. The latter exhibited rapidly progressive weakness of upper and lower limbs, neither upper motor neuron nor bulbar involvement, and shorter survival than typical ALS. We provide an accurate description of the phenotype, and a bioinformatics analysis of the p.V119M variant on protein structure. This study may increase the knowledge about genotype-phenotype correlations in ALS and improve the approach to ALS patients.

MRI DTI and PDFF as Biomarkers for Lower Motor Neuron Degeneration in ALS

ObjectiveTo evaluate the utility of nerve magnetic resonance imaging (MRI), diffusion tensor imaging (DTI), and muscle MRI multi-echo Dixon for assessing lower motor neuron (LMN) degeneration in amyotrophic lateral sclerosis (ALS).MethodsIn this prospective observational cohort study, 14 patients with ALS and 13 healthy controls underwent a multiparametric MRI protocol, including DTI of the sciatic nerve and assessment of muscle proton density fat fraction of the biceps femoris and the quadriceps femoris muscles by a multi-echo Dixon sequence.ResultsIn ALS patients, mean fractional anisotropy values of the sciatic nerve were significantly lower than those of healthy controls. The quadriceps femoris, but not the biceps femoris muscle, showed significantly higher intramuscular fat fractions in ALS.InterpretationOur study provides evidence that multiparametric MRI protocols might help estimate structural nerve damage and neurogenic muscle changes in ALS.