Bibrachial amyotrophy as a rare manifestation of intraspinal fluid collection: a case report and systematic review.

INTRODUCTION: Intraspinal cerebrospinal fluid (CSF) collection has been reported as a rare cause of lower motor neuron (LMN) disorder. We report a case of bibrachial diplegia associated with intraspinal CSF collection and perform a systematic literature review. PATIENT AND METHODS: A 52-year-old man developed a bibrachial amyotrophy over 6 years, confirmed by the presence of cervical subacute neurogenic changes at electromyography (EMG). Brain magnetic resonance imaging (MRI) revealed cerebral siderosis, while spine MRI showed a ventral longitudinal intraspinal fluid collection (VLISFC) from C2 to L2. No CSF leakage was localized at myelography; a conservative treatment was chosen. We searched for all published cases until 30th April 2023 and extrapolated data of 44 patients reported in 27 publications. RESULTS: We observed a male predominance, a younger disease onset compared to amyotrophic lateral sclerosis, and a quite long disease duration, highlighting a slow disease progression. LMN signs were more frequently bilateral, mostly involving C5-C6 myotomes. Around 61% of patients presented additional symptoms, but only three referred to a history of headache. Accordingly, CSF opening pressure was mostly normal. Spinal MRI revealed the presence of VLISFC and in some cases myelomalacia. EMG patterns displayed both chronic and subacute neurogenic change in the cervical region. The disease course mainly depended on the treatment choice, which was mostly represented by a surgical approach when a specific dural defect was detected by imaging. CONCLUSION: Bibrachial diplegia due to VLISFC can be a treatable cause of focal amyotrophy and presents some clinical and radiological "red flags" which cannot be missed by a clinical neurologist.

Prognostic value of EMG genioglossus involvement in amyotrophic lateral sclerosis.

OBJECTIVE: To evaluate the prognostic value of needle electromyography (EMG) genioglossus involvement in patients with amyotrophic lateral sclerosis (ALS) at diagnosis. METHODS: We separately explored the prognostic value of clinical bulbar lower motor neuron (LMN) signs and EMG genioglossus involvement using Cox proportional hazard models adjusted for age, gender, diagnostic delay, presence of bulbar upper motor neuron (UMN) signs, EMG cervical and lumbosacral region involvement, ALSFRS-R score and C9Orf72 gene status. Then, we compared the prognostic value of EMG masseter and genioglossus abnormalities in a subset of patients in whom both muscles were analysed. RESULTS: 103 ALS patients were included in the study. Neurophysiological genioglossus involvement was associated with a shorter survival (p = 0.002), a shorter time to moderate dysphagia (p = 0.0001) and to severe dysarthria (p = 0.012). Its prognostic value was still evident in patients without clinical bulbar LMN signs. Bulbar clinical LMN signs were only associated with an earlier onset of moderate dysphagia (p = 0.0001). EMG masseter abnormalities did not reach statistical significance with regard to all the clinical milestones. CONCLUSIONS: Genioglossus EMG at diagnosis could provide important information about ALS progression rate. The masseter muscle seems to be less involved in ALS. SIGNIFICANCE: EMG genioglossus involvement is a prognostic factor in ALS.

Comparison of ice pack test and single-fiber EMG diagnostic accuracy in patients referred for myasthenic ptosis.

OBJECTIVE: To compare the diagnostic accuracy of ice pack test (IPT) and single-fiber EMG (SF-EMG) in patients with suspected ocular myasthenia (OM) presenting with ptosis. METHODS: We studied consecutive patients referred for the clinical suspicion of OM. Patients underwent IPT and stimulated SF-EMG on the orbicularis oculi muscle. Receiver operating characteristic curve analysis was performed to determine the accuracy of IPT, SF-EMG, and their combination. RESULTS: We included 155 patients, 102 with OM and 53 with other diagnosis (OD). The IPT had a sensitivity of 86% (95% confidence interval [CI] 79-93) and a specificity of 79% (95% CI 68-90). SF-EMG showed a sensitivity of 94% (95% CI 89-98) and a specificity of 79% (95% CI 68-90). Overall, IPT and SF-EMG showed discordant results in 30 cases, 16 OM and 14 OD. The combination of IPT and SF-EMG, using the positivity of at least one test for OM diagnosis, increased the sensitivity to 98% (95% CI 95-100), reducing the specificity to 66% (95% CI 53-78), whereas using the positivity of both tests, we obtained a sensitivity of 82% (95% CI 75-90) and a specificity of 92% (95% CI 85-99). The negativity of both tests had a 94% (95% CI 87-100) negative predictive value. Comparison of the areas under the curve showed no differences in the diagnostic accuracy of IPT, SF-EMG, and their combinations. CONCLUSIONS: IPT and SF-EMG have similar diagnostic accuracy in patients with OM presenting with ptosis. The negativity of both tests strongly suggests another diagnosis. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that both the IPT and SF-EMG accurately identify patients with OM.

Diagnostic-prognostic value and electrophysiological correlates of CSF biomarkers of neurodegeneration and neuroinflammation in amyotrophic lateral sclerosis.

Neurofilament light chain protein (NfL) is currently the most accurate cerebrospinal fluid (CSF) biomarker in amyotrophic lateral sclerosis (ALS) in terms of both diagnostic and prognostic value, but the mechanism underlying its increase is still a matter of debate. Similarly, emerging CSF biomarkers of neurodegeneration and neuroinflammation showed promising results, although further studies are needed to clarify their clinical and pathophysiological roles. In the present study we compared the diagnostic accuracy of CSF NfL, phosphorylated (p)-tau/total (t)-tau ratio, chitinase-3-like protein 1 (YKL-40) and chitotriosidase 1 (CHIT1), in healthy controls (n = 43) and subjects with ALS (n = 80) or ALS mimics (n = 46). In ALS cases, we also investigated the association between biomarker levels and clinical variables, the extent of upper motor neuron (UMN) and lower motor neuron (LMN) degeneration, and denervation activity through electromyography (EMG). ALS patients showed higher levels of CSF NfL, YKL-40, CHIT1, and lower values of p-tau/t-tau ratio compared to both controls and ALS mimics. Among all biomarkers, NfL yielded the highest diagnostic performance (> 90% sensitivity and specificity) and was the best predictor of disease progression rate and survival in ALS. NfL levels showed a significant  correlation with the extent of LMN involvement, whereas YKL-40 levels increased together with the number of areas showing both UMN and LMN damage. EMG denervation activity did not correlate with any CSF biomarker change. These findings confirm the highest value of NfL among currently available CSF biomarkers for the diagnostic and prognostic assessment of ALS and contribute to the understanding of the pathophysiological and electrophysiological correlates of biomarker changes.

Sensitivity and specificity of single-fibre EMG in the diagnosis of ocular myasthenia varies accordingly to clinical presentation.

BACKGROUND AND PURPOSE: Single-fibre electromyography (SF-EMG) is considered as the most sensitive test for the diagnosis of MG. However, previous studies had limitations, such as a retrospective design, non-consecutive sampling, incorporation bias or were performed in small or mixed populations. Our aims were to determine the diagnostic sensitivity and specificity of SF-EMG of the orbicularis oculi in OMG and the utility of this test in relation to patients' clinical presentation. MATERIALS AND METHODS: We studied 232 consecutive patients referred to the SF-EMG laboratory for a suspected OMG. Stimulated SF-EMG was performed on the orbicularis oculi muscle. RESULTS: OMG was diagnosed in 165 cases and other disorders (OD) in 67. SF-EMG showed a sensitivity of 0.79 (95% CI 0.73-0.85) and a specificity of 0.80 (95% CI 0.71-0.90). False negative results were associated with mild symptoms and with isolated diplopia. Comparison of the diagnostic yield among patients with different clinical presentations showed a similar diagnostic accuracy of SF-EMG in patients with ptosis and in patients with ptosis and diplopia, significantly higher than in patients with isolated diplopia (P < 0.0001). Twenty-two patients with OMG presenting with isolated ptosis or diplopia, who initially tested negative, were re-tested in relation to a worsening of their symptoms showing a positivisation in 91% of cases. CONCLUSIONS: SF-EMG on the orbicularis oculi muscle is very sensitive in patients with ptosis. In contrast, in patients with isolated diplopia SF-EMG does not exclude OMG. Therefore, the interpretation of the results of the test should take into account the patients' clinical presentation.

Effects on cognition of 20-day anodal transcranial direct current stimulation over the left dorsolateral prefrontal cortex in patients affected by mild cognitive impairment: a case-control study.

BACKGROUND: Mild cognitive impairment (MCI) is a common disorder affecting as much as 15% of the elderly population. Transcranial direct current stimulation (tDCS) is a non-invasive technique of neuromodulation that has proven to influence performance in different cognitive domains. OBJECTIVE/HYPOTHESIS: We investigated the effects on cognition of 20-day anodal tDCS in 17 MCI patients compared with 17 matched MCI patients. METHODS: Patients underwent neuropsychological evaluation at baseline and then were randomly assigned to the anodal or sham group. The tDCS protocol consisted in 20 min, 5 days per week (up to a total of 20 days), of 2-mA anodal stimulation over the left dorsolateral prefrontal cortex (DLPFC). The location of anodal electrode was chosen in accordance with previous reports which relate anodal stimulation of this site with cognitive enhancement. At the end of the last day of stimulation, a second neuropsychological evaluation was performed. We compared baseline and post-stimulation neuropsychological results in the anodal vs sham group using repeated measures ANOVA as a statistical analysis test. RESULTS: At follow-up, patients exposed to anodal stimulation showed improvement in episodic verbal memory (p < 0.001) and figure naming test (p < 0.01), in a general index of cognitive function (Brief Mental Deterioration Battery) (p < 0.0001) and in a mood measurement test (Beck Depression Inventory) (p < 0.01). CONCLUSION: Anodal tDCS could be a useful tool to improve cognitive symptoms in MCI although more evidence is needed to understand the exact underlying mechanisms. Confirmation of its potential benefits in MCI would be significant.

Cognitive Rehabilitation and Transcranial Direct Current Stimulation in a Patient with Posterior Cortical Atrophy: An fMRI Study.

BACKGROUND Posterior cortical atrophy (PCA) is a neurodegenerative syndrome that accounts for 5% of the atypical presentation of Alzheimer disease (AD). To date, only a few studies have explored the effect of non-pharmacological treatment in PCA patients and no studies have evaluated the efficacy of transcranial direct current stimulation (tDCS) in this disorder. CASE REPORT A 58-year-old PCA patient underwent a cognitive rehabilitation treatment followed by 2 cycles of tDCS stimulation. The effects of both treatments were monitored over time with a standardized task-based fMRI protocol and with a neuropsychological assessment. Improvements in cognitive abilities, increased fMRI activation in the dorsolateral prefrontal cortex, and deactivation of the default mode network during the Stroop test performance were detected after each session treatment. CONCLUSIONS This combined approach lead to both cognitive improvements and neurophysiological adaptive changes, however, further studies on a larger cohort are needed to confirm these preliminary results.

Skin biopsy and I-123 MIBG scintigraphy findings in idiopathic Parkinson's disease and parkinsonism: a comparative study.

BACKGROUND: (123) I-meta-iodobenzylguanidine ((123) I-MIBG) myocardial scintigraphy is considered reliable in differentiating idiopathic Parkinson's disease (IPD) from other parkinsonisms, but it is biased by pharmacological treatments. Skin biopsy is not influenced by therapy and has disclosed skin denervation in IPD. Our aims were to compare (123) I-MIBG scintigraphy and skin biopsy findings in IPD and parkinsonisms to (1) verify whether myocardial and skin denervations are linked; (2) explore the simultaneous extent of the autonomic dysfunction. METHODS: We studied 22 IPD and 11 parkinsonism patients by means of (123) I-MIBG scintigraphy and skin biopsies. RESULTS: In the IPD group, both (123) I-MIBG scintigraphy and skin biopsy results were abnormal in 91% of patients, showing concordance in 82% of cases. In parkinsonisms, results of both tests were normal in all patients. CONCLUSION: (1) Skin biopsy and (123) I-MIBG scintigraphy provide comparable results; (2) in IPD, autonomic dysfunctions are often simultaneously widespread at cardiac and skin branches. © 2015 International Parkinson and Movement Disorder Society.

Peripheral autonomic neuropathy: diagnostic contribution of skin biopsy.

Skin biopsy has gained widespread use for the diagnosis of somatic small-fiber neuropathy, but it also provides information on sympathetic fiber morphology. We aimed to ascertain the diagnostic accuracy of skin biopsy in disclosing sympathetic nerve abnormalities in patients with autonomic neuropathy. Peripheral nerve fiber autonomic involvement was confirmed by routine autonomic laboratory test abnormalities. Punch skin biopsies were taken from the thigh and lower leg of 28 patients with various types of autonomic neuropathy for quantitative evaluation of skin autonomic innervation. Results were compared with scores obtained from 32 age-matched healthy controls and 25 patients with somatic neuropathy. The autonomic cutoff score was calculated using the receiver operating characteristic curve analysis. Skin biopsy disclosed a significant autonomic innervation decrease in autonomic neuropathy patients versus controls and somatic neuropathy patients. Autonomic innervation density was abnormal in 96% of patients in the lower leg and in 79% of patients in the thigh. The abnormal findings disclosed by routine autonomic tests ranged from 48% to 82%. These data indicate the high sensitivity and specificity of skin biopsy in detecting sympathetic abnormalities; this method should be useful for the diagnosis of autonomic neuropathy, together with currently available routine autonomic testing.

Microneurographic evaluation of sympathetic activity in small fiber neuropathy.

OBJECTIVE: Small fiber neuropathy (SFN) may involve somatic and autonomic fibers. Assessment of somatic epidermal nerve fiber density (ENFs) is considered the gold standard test in the diagnosis of SFN. By contrast, autonomic involvement in SFN is more difficult to ascertain. Here we investigate peripheral sympathetic outflow by microneurography in patients with selective small nerve fiber involvement of different origin with and without autonomic symptoms to ascertain the ability of microneurography and the corresponding skin organ effector responses (sympathetic skin activity-SSR and skin vasomotor reflex-SVR) to disclose autonomic involvement. METHODS: We studied 59 patients with SFN because of reduced leg ENFs and normal conduction studies. Thirty patients reported only burning paresthesia (somatic SFN) whereas 29 patients complained of additional autonomic dysfunctions (autonomic SFN). They underwent microneurography from peroneal nerve with the recording of muscle sympathetic nerve activity (MSNA), skin sympathetic nerve activity (SSNA) and the corresponding SSR and SVR in the same innervation field. Thirty age and sex-matched healthy subjects served as controls. RESULTS: Patients with autonomic SFN mainly complained of loss of sweating. They showed a significant absence of indirect (SSR and SVR) and direct (MSNA and SSNA) sympathetic tests compared to somatic SFN patients and controls. SSNA, SSR and SVR were more often absent than MSNA. In addition, SSR and SVR were absent in all patients with no recordable SSNA but no significant relationship was found with MSNA recording. CONCLUSIONS: SSR and SVR, simple indirect tests of sympathetic activity, could help to disclose autonomic involvement in SFN with a good sensitivity mainly in patients with sweating dysfunctions although they expressed autonomic failure in only one sympathetic branch. SIGNIFICANCE: Microneurographic evaluation of sympathetic activity, technically more difficult than indirect tests, was a useful functional tool contributing to the diagnosis and extension of autonomic involvement in SFN. Our data showed that the skin sympathetic branch is more often involved than the muscle sympathetic branch in SFN.

Somatic and autonomic small fiber neuropathy induced by bortezomib therapy: an immunofluorescence study.

Bortezomib is a new chemotherapeutic agent approved for the treatment of relapsed/refractory and newly diagnosed multiple myeloma. One of the major side effects of bortezomib is a peripheral length-dependent sensory axonal neuropathy and, less frequently, a small fiber neuropathy. Autonomic symptoms like postural dizziness, syncope, diarrhoea, ileus, impotence and urinary disturbances have been reported, nevertheless, autonomic neuropathy has never been characterized. We describe by means of immunofluorescence, the involvement of autonomic skin nerve fibers in three patients with small fiber neuropathy induced by bortezomib treatment.

Small fiber neuropathy in female patients with fabry disease.

Recent studies suggest that heterozygous female Fabry disease (FD) patients develop peripheral neuropathy. We used skin biopsy to define somatic and autonomic peripheral nerve characteristics in 21 females with FD who were mainly asymptomatic and had normal renal function. Somatic epidermal and dermal autonomic nerve fiber reductions were found, prevalently in the leg, and no differences were found between symptomatic and asymptomatic individuals. Our findings suggest that females with FD, although asymptomatic, may have somatic and autonomic small fiber neuropathy.