Risk factors of asymptomatic reduction of motor conduction velocity of the ulnar nerve across the elbow.

INTRODUCTION: The aim of the study was to check the risk factors for subjects with motor conduction velocity (MCV) reduction of the ulnar nerve across the elbow without symptoms/signs of ulnar neuropathy at the elbow (UNE) using a database of a previous multicenter case-control study on UNE patients. METHODS: From the previous database, we extracted all asymptomatic UNE (A-UNE) and matched for age and sex with a control and UNE groups with a ratio of 1:2. Anthropometric factors were measured and all participants filled in a questionnaire on demographic, lifestyle factors, and medical history. One-sample proportion test and univariate and multivariate logistic regression analyses were performed. RESULTS: We enrolled 64 A-UNE, 124 UNE, and 124 controls (mean age 53 years). There were more males with A-UNE than females (74.2%). The predominantly or exclusively concerned side of A-UNE was the right. Logistic regression showed that A-UNE was associated with diabetes (OR = 2.99, 95% CI = 1.21-7.39) and width of cubital groove (CGW) (OR = 0.89, 95%  CI = 0.81-0.97). DISCUSSION: Risk factors for A-UNE are different from UNE. The prevalence of right side in A-UNE was not due to particular elbow postures. Diabetes is a risk factor, probably because MCV reduction of the ulnar nerve across the elbow was an early manifestation of asymptomatic polyneuropathy in diabetes. A-UNE is associated with narrow CGW as already demonstrated in UNE, even if the OR was higher in UNE than in A-UNE. Only future longitudinal studies will be able to check whether the A-UNE subjects develop symptoms and signs of true mononeuropathy with time.

A case of spastic paraplegia type 11 mimicking a GM2-gangliosidosis.

INTRODUCTION: Spastic paraplegia type 11 (SPG11) is the most frequent autosomal recessive HSP. Studies on SPG11 patients' fibroblasts, post-mortem brains, and mouse models revealed endolysosomal system dysfunction and lipid accumulation, especially gangliosides. We report a patient with early clinical findings mimicking a GM2-gangliosidosis. METHODS: A clinical, biochemical, and metabolic characterization was performed. Electron microscopy analysis was completed on rectal mucosa and skin biopsy specimens. A NGS panel of genes associated to neuronal ceroid lipofuscinosis and HSP was analyzed. RESULTS: The patient presented with worsening walking difficulty and psychomotor slowdown since childhood; to exclude a neurometabolic storage disease, skin and rectal biopsies were performed: enteric neurons showed lipofuscin-like intracellular inclusions, thus suggesting a possible GM2-gangliosidosis. However, further analysis did not allow to confirm such hypothesis. In adulthood we detected flaccid paraplegia, nystagmus, axonal motor neuropathy, carpus callosum atrophy, and colon atony. Surprisingly, the NGS panel detected two already reported SPG11 mutations in compound heterozygosity. CONCLUSIONS: We describe for the first time pathological hallmarks of SPG11 in enteric neuron from a rectal mucosa biopsy. The report illustrates the possible overlap between SPG11 and GM2-gangliosidosis, especially in the first disease phases and helps to improve our knowledge about SPG11 physiopathology.

Comorbidities, anthropometric, demographic, and lifestyle risk factors for ulnar neuropathy at the elbow: A case control study.

We performed a prospective multicenter case-control study to explore the association between ulnar neuropathy at elbow (UNE) and body and elbow anthropometric measures, demographic and lifestyle factors, and comorbidities. Cases and controls were consecutively enrolled among subjects admitted to four electromyography labs. UNE diagnosis was made on clinical and neurographic findings. The control group included all other subjects without signs/symptoms of ulnar neuropathy and with normal ulnar nerve neurography. Anthropometric measurements included weight, height, waist, hip circumferences, and external measures of elbow using a caliper. The participants filled in a self-administered questionnaire on personal characteristics, lifestyle factors, and medical history. We estimated odds ratios (ORs) and 95% confidence intervals (CIs) by fitting unconditional logistic regression models adjusted by center and education level. We enrolled 220 cases (males 61.8%; mean age 51.7 years) and 460 controls (47.4% males; mean age 47.8 years). At multivariable analysis, UNE was associated to male gender (OR = 2.4, 95%CI = 1.6-3.7), smoking habits (>25 pack-years (OR = 2.3, 95%CI = 1.3-4.1), body mass index (OR = 1.05, 95%CI 1.01-1.10), polyneuropathies (OR = 4.1, 95%CI 1.5-11.5), and leaning with flexed elbow on a table/desk (OR = 1.5, 95%CI 1.0-2.2). Cubital groove width (CGW) turned out to be negatively associated with UNE (OR = 0.80, 95%CI = 0.74-0.85). Our study suggests that some personal factors especially anthropometric measures of the elbow may play a role in UNE pathogenesis as the measures of wrist in CTS. We demonstrated that for each millimeter of smaller CGW the risk of idiopathic UNE increases of 25%.

The external elbow measure as surrogate of the anatomical width of cubital groove and possible risk factor of ulnar neuropathy at the elbow.

Introduction: There are no studies on elbow anthropometry in ulnar neuropathy at the elbow (UNE). We aimed to test the interrater agreement of external elbow measurements with caliper, the matching of external width of cubital groove (WCG) measures with those obtained through conventional radiography (XR) and ultrasonography (US). The final aim was to evaluate the differences of anthropometric elbow and body measures between UNE cases and controls with multicenter prospective study.Materials and methods: After common training of five observers for external elbow and body anthropometric measurements, we assessed the interrater agreement of measures in a single blind measurement session in 16 healthy volunteers. Then we verified if external WCG measures in eight and four of the above 16 subjects matched with those obtained with US and XR. Finally, we enrolled 40 consecutive idiopathic UNE cases in four electromyographic labs matched for sex and age with 40 controls to evaluate the differences of anthropometric measures.Results: There was high interrater agreement of all anthropometric body and elbow measures (Kendal's and interclass correlation coefficients between 0.84 and >0.9). We found high relations between WCG caliper measures and those obtained with US and XR (r > 0.9). WCG was smaller in cases than in controls (13.2 vs.15.7 mm, p < 0.001). There were no differences in body anthropometric measures (BMI and waist-to-hip ratio).Conclusion: The external measurement of WCG is reliable and reproducible and may be risk factor of UNE. Future studies should be performed in lager samples evaluating the relations with lifestyle and occupational factors.

Clinical Features and Outcome of the Guillain-Barre Syndrome: A Single-Center 11-Year Experience.

Background: Clinical presentation, electrophysiological subtype, and outcome of the Guillain-Barre' Syndrome (GBS) may differ between patients from different geographical regions. This study aims to assess clinical-neurophysiological features of an adult, Italian GBS cohort over 11 years. Methods: Retrospective (from 1 January 2011 to 31 December 2021) analysis was carried out on patients admitted to the Siena University Hospital who fulfilled the GBS diagnostic criteria. Demographic data, clinical characteristics, treatment, need of mechanical ventilation (MV), laboratory and electrophysiological tests, preceding infections/vaccination/other conditions, and comorbidities were collected for each patient. Results: A total of 84 patients (51 men, median age of 61 years), were identified. GBS subtype was classified as acute inflammatory demyelinating polyneuropathy (AIDP) in the 66.6% of patients, acute motor/sensory axonal neuropathy (AMAN/AMSAN) in 20.2%, and the Miller Fisher syndrome in 5 (5.9%). Flu syndrome and gastrointestinal infection were the most common preceding conditions. In total, five (5.9%) subjects had concomitant cytomegalovirus (CMV) infection. Cranial nerve involvement occurred in 34.5% of subjects. Differences between the axonal and AIDP forms of GBS concerned the presence of anti-ganglioside antibodies. In total, seven (8.33%) patients required MV. Discussion: The epidemiological and clinical characteristics of GBS in different countries are constantly evolving, especially in relation to environmental changes. This study provides updated clinical-epidemiological information in an Italian cohort.

Clinical Findings and Electrodiagnostic Testing in Ulnar Neuropathy at the Elbow and Differences According to Site and Type of Nerve Damage.

OBJECTIVE: The aim of the study was to evaluate the clinical and electrodiagnostic testing in ulnar neuropathy at the elbow and differences according to site (humeroulnar arcade vs. retroepicondylar groove) and injury physiopathology (axonal vs. demyelinating), through prospective multicenter case-control study. DESIGN: Cases and controls were matched by age and sex. Ulnar neuropathy at the elbow diagnosis was made on symptoms. Statistical analysis was performed using Mann-Whitney, χ, and analysis of variance tests. RESULTS: One hundred forty-four cases and 144 controls were enrolled. Sensory loss in the fifth finger had the highest sensitivity (70.8%) compared with clinical findings. Motor conduction velocity across elbow reached the highest sensitivity (84.7%) in localizing ulnar neuropathy at the elbow recording from at least one of the two hand muscles (first dorsal interosseous and abductor digiti minimi). Abnormal sensory action potential amplitude from the fifth finger occurred more frequently in axonal than in demyelinating forms. Differences between retroepicondylar groove and humeroulnar arcade regarded conduction block and job type. CONCLUSIONS: Clinical findings have less usefulness than electrodiagnostic testing in ulnar neuropathy at the elbow diagnosis. Motor conduction velocity across elbow recorded from both abductor digiti minimi and first dorsal interosseous increases diagnostic accuracy. Axonal forms have greater clinical and electrodiagnostic testing severity than demyelinating forms, which are more frequent in retroepicondylar groove. Manual workers prevailed in humeroulnar arcade. These findings may be helpful in prognostic and therapeutic approaches.

Liver transplantation in mitochondrial neurogastrointestinal encephalomyopathy (MNGIE): clinical long-term follow-up and pathogenic implications.

We report the longest follow-up of clinical and biochemical features of two previously reported adult mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) patients treated with liver transplantation (LT), adding information on a third, recently transplanted, patient. All three patients overcame the early post-operative period and tolerated immunosuppressive therapy. Plasma nucleoside levels dramatically decreased, with evidence of clinical improvement of ambulation and neuropathy. Conversely, other features of MNGIE, as gastrointestinal dysmotility, low weight, ophthalmoparesis, and leukoencephalopathy were essentially unchanged. A similar picture characterized two patients treated with allogenic hematopoietic stem cell transplantation (AHSCT). In conclusion, LT promptly and stably normalizes nucleoside imbalance in MNGIE, stabilizing or improving some clinical parameters with marginal periprocedural mortality rate as compared to AHSCT. Nevertheless, restoring thymidine phosphorylase (TP) activity, achieved by both LT and AHSCT, does not allow a full clinical recovery, probably due to consolidated cellular damage and/or incomplete enzymatic tissue replacement.

Rapidly progressive neurodegeneration in a case with the 7472insC mutation and the A7472C polymorphism in the mtDNA tRNA ser(UCN) gene.

The authors report the clinical, neuroimaging, muscle biopsy and mtDNA findings in a patient affected by bilateral hearing loss and mental retardation since infancy, presenting at age 31 years with a rapid deterioration of mental status and ataxia leading to vegetative condition and death at the age of 32 years. Clinical and genetic studies have been also performed in the mother, affected by neurosensorial hearing loss. Muscle biopsy showed severe mitochondrial alterations in the propositus and evidence of mitochondrial alterations in his mother. Direct mtDNA sequencing in all family members revealed the known 7472insC mutation and the recently described A7472C sequence variation in the tRNA(Ser(UCN))gene. RFLP-PCR confirmed the heteroplasmic nature of the two mutations and failed to find the second transversion in 200 controls. The percentage of mutant genomes harbouring 7472insC ranged from 3 to 7% in asymptomatic family members to 70% in the proband and his mother, whereas the percentage of A7472C mutant genomes was about 90% in all maternal relatives except the proband (56%) and his sister (5%). In conclusion, this is the first report of a rapidly progressive encephalopathy in association with the 7472insC mutation in mtDNA, combined with an A>C variation at the same nucleotide with a possible suppression effect on the pathogenic mutation.

Peripheral neuropathy in CADASIL.

BACKGROUND: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy (CADASIL) is a hereditary cerebral microangiopathy associated with mutations in the Notch 3 gene. The clinical phenotype is characterized by cerebral impairment even though typical microvascular changes are diffuse. OBJECTIVE: To assess peripheral neuropathy in patients with CADASIL. PATIENTS AND METHODS: We enrolled eleven CADASIL patients with variable phenotype including clinical signs of peripheral nerve involvement. In all patients electromyography and nerve conduction velocities were performed. Peripheral nerve biopsy was performed in three cases. RESULTS: We found sensory motor neuropathy in 7/11 patients. Nerve biopsy revealed axonal and demyelinated findings. CONCLUSION: Our findings suggest that peripheral neuropathy may be part of the CADASIL phenotype.

Acute unilateral visual loss as the first symptom of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy.

BACKGROUND: Although cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is considered a cerebrovascular disorder with almost exclusively neurological symptoms, the arteriopathy is generalized and involves choroidal and retinal vasculature as demonstrated by fluorescein angiographic and ocular electrophysiological abnormalities. The occurrence of acute visual loss due to nonarteritic anterior ischemic optic neuropathy (NAION) has not previously been reported in CADASIL. OBJECTIVE: To describe acute visual loss due to NAION as a possible manifestation of CADASIL. PATIENTS AND METHODS: The patient was a 60-year-old man with subcortical diffuse leukoencephalopathy, multi-infarct dementia, tetraparesis, visual loss, and a family history of stroke. We performed clinical and neuro-ophthalmological evaluation, electrophysiological assessment, brain magnetic resonance imaging, and genetic screening for mutations or small deletions of the Notch3 gene, (causing CADASIL). RESULTS: The patient's first symptom was acute visual loss in the right eye due to NAION at age 27 years, in absence of the common cardiovascular risk factors and before any neurological impairment. The patient was reevaluated at age 60 years, and neuro-ophthalmological examination showed optic disc atrophy in the right eye with arteriolar narrowing and a reduction in visual acuity in the left eye. Fluorescein angiography of the right eye showed evidence of persistent peripapillary hypofluorescence with a retinal pigment epithelial windows defect in the inferior temporal area. Pattern reversal visual evoked potentials were abolished in the right eye. The P100 latency of the left eye was delayed and reduced in amplitude. The diagnosis of CADASIL was confirmed by molecular analysis (heterozygotes for the C406T mutation on exon 3 of the Notch3 gene). There was a family history of cerebrovascular disorders and ocular impairment. CONCLUSIONS: Visual loss due to transient or stable ischemic events involving the optic nerve head should be considered in the CADASIL phenotype. The possibility of CADASIL should also be evaluated in patients with NAION who do not have cardiovascular risk factors but do have a family history of stroke.

MR evidence of structural and metabolic changes in brains of patients with Werner's syndrome.

OBJECTIVE: To assess CNS abnormalities in patients with Werner's syndrome (WS) using MR metrics specific for tissue damage. BACKGROUND: WS is a rare autosomal recessive disorder that causes premature aging. The CNS involvement in this disease is still debated. METHODS: Two siblings who showed signs of neurological involvement underwent MR spectroscopic imaging (MRSI) and magnetization transfer (MT) imaging. Also, on conventional T1-weighted MR images, measurements of total brain volume were performed. RESULTS: Conventional MR images of both WS patients did not show abnormalities on visual inspection. However, both WS patients showed significantly lower values of normalized total brain volume and MT ratio in the white matter than age-matched normal controls. Also, proton MRSI showed significantly lower values of central brain NAA/Cr in WS patients than in normal controls. CONCLUSIONS: Our findings suggest that, despite normal appearance on conventional MRI, diffuse structural and metabolic tissue damage can be demonstrated in WS brains by means of sensitive MR methods even in patients with moderate or subclinical CNS involvement.

Protocol of outcome evaluation for surgical release of carpal tunnel syndrome.

OBJECTIVE: To propose and apply a protocol for assessing the outcome of surgery for carpal tunnel syndrome. METHODS: The protocol included a patient questionnaire that was self-administered before and 1 and 6 months after the operation to assess severity of symptoms (Boston questionnaire) and staging according to clinical (Giannini) and electrophysiological (Padua) severity scales. RESULTS: The results of a prospective series of 323 hands undergoing surgery for carpal tunnel syndrome by the mini-incision of the palm technique are reported. CONCLUSION: The method was found to be valid, precise, reliable, and straightforward, enabling a comparison of the results from different patient series and different operating techniques.

The first Italian patient with oculopharyngodistal myopathy: case report and considerations on differential diagnosis.

Oculopharyngodistal myopathy is a clinicopathologically distinct muscular disease. The underlying genetic defect has not been identified. We report here a 43-year old woman with asymmetric bilateral ptosis, dysphonia, swallowing difficulties, and weakness of the distal leg muscles. Serum creatine kinase was moderately increased. Electromyography revealed myopathic changes and myotonic discharges. Both cardiologic and pneumologic evaluation did not reveal abnormalities. Muscle computed tomography images showed adipose tissue replacement of abdominis rectus, lateral vastus, adductor magnus, and both the posterior and anterior compartment muscles below the knee, with prevalent involvement of medial gastrocnemius muscle. Muscle biopsy uncovered changes in fiber size and the presence of atrophic fibers with rimmed vacuoles of varying diameter, and core-like structures in type I fibers. Diagnosis was performed according to clinical and histopathologic findings, which were fully consistent with the other reported patients, and on the genetic exclusion of similar conditions such as oculopharyngeal muscular dystrophy, myotonic dystrophy type 1 and multi-minicore disease associated to RYR1 mutations. Differential diagnosis with mitochondrial myopathies, facioscapulohumeral muscular dystrophy and distal myopathies was also considered. This is the first Italian case of oculopharyngodistal myopathy, further suggesting the worldwide distribution of this rare neuromuscular disorder.

Neuromyotonia as paraneoplastic manifestation of bladder carcinoma.

Neuromyotonia(NMT) or Isaacs syndrome is a rare syndrome characterized by continuous spontaneous muscle fiber contraction resulting from hyperexcitability of peripheral nerves often associated with autoimmune disorders and tumours. Here we report an unpublished association of NMT and bladder cancer.