Search Results (12)

Background: Small-fiber neuropathy (SFN), affecting Aδ or C nerve fibers, is characterized by alterations of pain and temperature sensation, as well as autonomic dysfunction. Its diagnosis may still remain challenging as methods specifically assessing small nerve fibers are not always readily available, and standard techniques for large-fiber neuropathies, such as electroneuromyography, yield negative results. Still, skin biopsy for epidermal innervation and quantitative sensory testing allow for diagnosis in the presence of a congruent clinical picture. Objectives: Many different etiologies may underlie small-fiber neuropathy, of which metabolic (diabetes mellitus/impaired glucose tolerance) and idiopathic remain prevalent. The aim of this narrative review is to provide a general picture of SFN while focusing on the different etiologies described in the literature in order to raise awareness of the variegated set of different causes of SFN and promote adequate diagnostic investigation. Methods: The term “Small-Fiber Neuropathy” was searched on the PubMed database with its different recognized etiologies: the abstracts of the articles were reviewed and described in the article if relevant for a total of 40 studies. Results: Many different disorders have been associated with SFN, even though often in the form of case reports or small case series. Conclusions: Idiopathic forms of SFN remain the most prevalent in the literature, but association with different disorders (e.g., infectious, autoimmune) should prompt investigation for SFN in the presence of a congruent clinical picture (e.g., pain with neuropathic features). Full article

Background: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder, and although the diagnosis is primarily based on clinical criteria, ENMG, as the “gold standard”, does not always show detectable changes. Therefore, our study suggests that alterations in echogenicity and heterogeneity of the phrenic nerve (PN) may serve as potential additional diagnostic tools for ALS. Methods: Our study included 32 patients in the ALS group and 64 individuals in the control group. Each participant underwent an interview and completed questionnaires to collect clinical and demographic data, including age, gender, height, body mass index (BMI), hip and waist circumference, duration of illness, ALS-FRS-R score, comorbidities, and medication use. Ultrasound examinations of the PN were performed by two authors using a high-resolution “Philips EPIQ 7” ultrasound machine equipped with a linear 4–18 MHz transducer. The ALS group participants underwent PN sonography and conduction examinations, arterial blood gas (ABG) analysis, respiratory function tests (RFT), and electroneuromyography (ENMG). Results: The study demonstrated that the phrenic nerve is significantly smaller on both sides in patients with ALS compared to the control group (p < 0.01). Changes in the homogeneity and echogenicity of the PN were also observed on both sides. On the right side, 43.8% of the nerves showed heterogeneity, 40.6% were isoechoic, and 21.9% were hyperechoic. On the left side, 59.4% of the nerves exhibited heterogeneity, 34.4% were isoechoic, and 28.1% were hyperechoic. Moreover, sonography on both sides showed significant correlation with ALS-FRS-R, COMPASS-31, and ENMG results. Conclusions: Our study highlights the importance of phrenic nerve ultrasound as a promising supplementary diagnostic tool for ALS. The significant differences in phrenic nerve size, echogenicity, and homogeneity between patients with ALS and the control group demonstrate that ultrasound imaging can detect morphological changes in the phrenic nerve. Incorporating phrenic nerve ultrasound into routine diagnostic protocols could improve early detection, enhance disease monitoring, and offer a more comprehensive understanding of the neurodegenerative processes in ALS. Full article

Background/Objectives: The accurate quantification of peripheral nerve axonal regeneration after injury is critically important. Current strategies are limited to detecting early reinnervation. DTI is an MRI modality permitting the assessment of fractional anisotropy, which increases with axonal regeneration. The aim of this pilot study is to evaluate DTI as a potential predictive factor of clinical outcome after median nerve section and microsurgical repair. Methods: We included 10 patients with a complete section of the median nerve, who underwent microsurgical repair up to 7 days after injury. The follow-up period was 1 year, including the current strategy with clinical visits, the Rosén–Lundborg score and electroneuromyography. Additionally, DTI MRI of the injured wrist was planned 1, 3 and 12 months post-operatively and once for the contralateral wrist. Results: The interobserver reliability of DTI measures was almost perfect (ICC 0.802). We report an early statistically significant increase in the fractional anisotropy value after median nerve repair, especially in the region located distal to the suture. Meanwhile, Rosén–Lundborg score gradually increased between the third and sixth month, and continued to increase between the sixth and twelfth month. Conclusions: DTI outcomes three months post-operation could offer greater predictability compared to current strategies. This would enable faster decision-making regarding the need for a potential re-operation in cases of inadequate early reinnervation. Full article

We investigate the etiology of amyotrophic lateral sclerosis (ALS) in a 35-year-old woman presenting with progressive weakness in her left upper limb. Prior to sequencing, a comprehensive neurological work-up was performed, including neurological examination, electrophysiology, biomarker assessment, and brain and spinal cord MRI. Six months before evaluation, the patient experienced weakness and atrophy in her left hand, accompanied by brisk reflexes and Hoffman sign in the same arm. Electroneuromyography revealed lower motor neuron involvement in three body regions. Neurofilament light chains were elevated in her cerebrospinal fluid. Brain imaging showed asymmetrical T2 hyperintensity of the corticospinal tracts and T2 linear hypointensity of the precentral gyri. Trio genome sequencing identified a likely pathogenic de novo variant in the KIF1A gene (NM_001244008.2): c.574A>G, p.(Ile192Val). Pathogenic variants in KIF1A have been associated with a wide range of neurological manifestations called KIF1A-associated neurological diseases (KAND). This report describes a likely pathogenic de novo variant in KIF1A associated with ALS, expanding the phenotypic spectrum of KAND and our understanding of the pathophysiology of ALS. Full article

Carpal tunnel syndrome (CTS) is the most common cause of peripheral compressive neuropathy and consists of compression of the median nerve in the wrist. Although there are several etiologies, idiopathic is the most prevalent origin, and among the forms of treatment for CTS, conservative is the most indicated. However, despite the high prevalence in and impact of this syndrome on the healthcare system, there are still controversies regarding the best therapeutic approach for patients. Therefore, noting that some studies point to vitamin D deficiency as an independent risk factor, which increases the symptoms of the syndrome, this study evaluated the role of vitamin D supplementation and its influence on pain control, physical examination and response electroneuromyography to conservative treatment of carpal tunnel syndrome. For this, the sample consisted of 14 patients diagnosed with CTS and hypovitaminosis D, who were allocated into two groups. The control group received corticosteroid treatment, while the experimental group received corticosteroid treatment associated with vitamin D. Thus, from this study, it can be concluded that patients who received vitamin D, when compared to those who did not receive it, showed improvement in the degree of pain intensity, a reduction in symptom severity and an improvement in some electroneuromyographic parameters. Full article

(1) Background: panic attack is often regarded as a benign disorder with variable physical and psychological symptoms. (2) Case Presentation: We here report the case of a 22-year-old patient known for an episode of motor functional neurological disorder a year earlier who presented a panic attack with hyperventilation causing severe hypophosphatemia and rhabdomyolysis, as well as mild tetraparesis. Electrolyte disturbances quickly resolved after phosphate substitution and rehydration. However, clinical signs suggesting a relapse of a motor functional neurological disorder appeared (improved walking with dual tasks). Diagnostic workup, including brain and spinal magnetic resonance imaging, as well as electroneuromyography and genetic testing for hypokalemic periodic paralysis, was unremarkable. Tetraparesis, lack of endurance, and fatigue eventually improved after several months. (3) Conclusions: the present case report highlights the intertwined relationship between a psychiatric disorder, leading to hyperventilation and acute metabolic disturbances, and functional neurological manifestations. Full article

This retrospective chart review study explored the etiology, use, and yield of the etiological investigations of 651 children and adolescents diagnosed with borderline intellectual functioning (BIF). Neurological, neurodevelopmental, or neuropsychiatric comorbidities were frequent, and in 23%, the BIF diagnosis evolved into an intellectual disability (ID) by the time of discharge. A primary etiological cause was found in 37.6%, the most prevalent causes being pre- or perinatal conditions, genetic syndromes/chromosomal abnormalities, fetal exposure to maternal substance use, cerebral dysgenesis, and neurological diseases. In total, 79.1% of patients went through one or more investigations during their follow-up. The best etiologic yield leading to a diagnosis in this study population was with exome sequencing, a specific gene panel, microarrays, electroneuromyography, and brain magnetic resonance imaging (MRI). Etiological investigations were performed more frequently among those children receiving an ID diagnosis. Yet, there was no statistically significant difference in the proportion of abnormal findings between the BIF and ID groups. This may mean that the current strategy for determining the need for etiological investigations or current means to gain an etiology is still indecisive. Considering that BIF is defined to include individuals performing between normal cognitive functioning and mild ID, this implies that the prevalence would be anywhere between 7 and 14%. Thus, it could be argued whether in-depth etiological investigations may be justified in cases other than ID in this age group of children over five. With these children and adolescents, the clinicians have to discern between those with a normal variation and those having major difficulties in adaptive behavior affecting everyday life in order to specify and prescribe the rehabilitation or other measures needed. We advocate for a targeted etiological search after careful history-taking and neurological examination. National guidelines that take into account the severity of developmental delay are warranted. Full article

X-linked Myopathy with Excessive Autophagy (XMEA) is a rare autophagic vacuolar myopathy caused by mutations in the Vacuolar ATPase assembly factor VMA21 gene; onset usually occurs during childhood and rarely occurs during adulthood. We described a 22-year-old patient with XMEA, whose onset was declared at 11 through gait disorder. He had severe four-limb proximal weakness and amyotrophy, and his proximal muscle MRC score was between 2 and 3/5 in four limbs; creatine kinase levels were elevated (1385 IU/L), and electroneuromyography and muscle MRI were suggestive of myopathy. Muscle biopsy showed abnormalities typical of autophagic vacuolar myopathy. We detected a hemizygous, unreported, intronic, single-nucleotide substitution c.164-20T>A (NM_001017980.4) in intron 2 of the VMA21 gene. Fibroblasts derived from this patient displayed a reduced level of VMA21 transcripts (at 40% of normal) and protein, suggesting a pathogenicity related to an alteration of the splicing efficiency associated with an intron retention. This patient with XMEA displayed a severe phenotype (rapid weakness of upper and lower limbs) due to a new intronic variant of VMA21, related to an alteration in the splicing efficiency associated with intron retention, suggesting that phenotype severity is closely related to the residual expression of the VMA21 protein. Full article

Neurogenic thoracic outlet syndrome (NTOS) is a disabling condition. Its diagnosis remains challenging and is mainly guided by examination. Yet, electrophysiological evaluations are the gold standard for diagnosis of entrapment syndromes. We aimed to assess the interest of electrophysiological evaluation to diagnose NTOS. A systematic literature research was performed using PubMed, ScienceDirect, Embase, Cochrane and Google Scholar databases to collect studies reporting results of electrophysiological assessment of patients with NTOS. Then, a meta-analysis was conducted. Nine studies were eligible and concerned two hundred and thirteen patients. Results were heterogenous among studies and the quality of evidence was very low to moderate. Data could not evaluate sensitivity or specificity of electrophysiological evaluations for NTOS. The meta-analysis found significantly decreased amplitudes of medial antebrachial cutaneous nerve SNAP (sensory nerve action potential), ulnar SNAP, median CMAP (compound motor action potential) and ulnar CMAP. Needle examination found abnormalities for the abductor pollicis brevis, first dorsal interosseous and adductor digiti minimi. Unlike most upper-limb entrapment syndromes, nerve conduction assessment only provided clues in favour of NTOS. Decreased amplitude for ulnar SNAP, medial antebrachial cutaneous SNAP, median CMAP and ulnar CMAP should be assessed, as well as needle examination. Larger studies are needed to evaluate the sensitivity and specificity of electrophysiology in NTOS diagnosis. Full article

CHMP2B is a protein that coordinates membrane scission events as a core component of the ESCRT machinery. Mutations in CHMP2B are an uncommon cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), two neurodegenerative diseases with clinical, genetic, and pathological overlap. Different mutations have now been identified across the ALS-FTD spectrum. Disruption of the neuromuscular junction is an early pathogenic event in ALS. Currently, the links between neuromuscular junction functionality and ALS-associated genes, such as CHMP2B, remain poorly understood. We have previously shown that CHMP2B transgenic mice expressing the CHMP2B^intron5 mutant specifically in neurons develop a progressive motor phenotype reminiscent of ALS. In this study, we used complementary approaches (behavior, histology, electroneuromyography, and biochemistry) to determine the extent to which neuron-specific expression of CHMP2B^intron5 could impact the skeletal muscle characteristics. We show that neuronal expression of the CHMP2B^intron5 mutant is sufficient to trigger progressive gait impairment associated with structural and functional changes in the neuromuscular junction. Indeed, CHMP2B^intron5 alters the pre-synaptic terminal organization and the synaptic transmission that ultimately lead to a switch of fast-twitch glycolytic muscle fibers to more oxidative slow-twitch muscle fibers. Taken together these data indicate that neuronal expression of CHMP2B^intron5 is sufficient to induce a synaptopathy with molecular and functional changes in the motor unit reminiscent of those found in ALS patients. Full article

Molecular defects in type 1 facioscapulohumeral muscular dystrophy (FSHD) are caused by a heterozygous contraction of the D4Z4 repeat array from 1 to 10 repeat units (RUs) on 4q35. This study compared (1) the phenotype and severity of FSHD1 between patients carrying 6–8 vs. 9–10 RUs, (2) the amount of methylation in different D4Z4 regions between patients with FSHD1 with different clinical severity scores (CSS). This cross-sectional multicenter study was conducted to measure functional scales and for genetic analysis. Patients were classified into two categories according to RUs: Group 1, 6–8; Group 2, 9–10. Methylation analysis was performed in 27 patients. A total of 99 carriers of a contracted D4Z4 array were examined. No significant correlations between RUs and CSS (r = 0.04, p = 0.73) and any of the clinical outcome scales were observed between the two groups. Hypomethylation was significantly more pronounced in patients with high CSS (>3.5) than those with low CSS (<1.5) (in DR1 and 5P), indicating that the extent of hypomethylation might modulate disease severity. In Group 1, the disease severity is not strongly correlated with the allele size and is mostly correlated with the methylation of D4Z4 regions. Full article

Fasciculations are visible, fine and fast, sometimes vermicular contractions of fine muscle fibers that occur spontaneously and intermittently. The aim of this article is to discuss the main causes for fasciculations and their pathophysiology in different sites of the central/peripheral injury and in particular to disprove that the presence of this finding in the neurological examination is indicative of amyotrophic lateral sclerosis. Undoubtedly, most fasciculations have a distal origin in the motor nerve both in normal subjects and in patients with motor neuron disease. Most of them spread to other dendritic spines often producing an antidromic impulse in the main axon. The clinical and neurophysiological diagnosis must be thorough. It may often take long to record fasciculations with electroneuromyography. In other cases, temporal monitoring is necessary before the diagnosis. The treatment, which may be adequate in some cases, is not always necessary Full article