Sandroni, Paola

Abstract Introduction/Aims Carpal and cubital tunnel syndrome (CTS, CuTS) are common among patients with hereditary neuropathy with liability to pressure‐palsies (HNPP) and Charcot–Marie‐Tooth type 1A (CMT1A) and may impact quality of life. We aimed to evaluate the utility of nerve decompression surgeries in these patients. Methods Medical records were reviewed for patients with PMP22 mutations confirmed in Mayo Clinic laboratories from January 1999 to December 2020, who had CTS and CuTS and underwent surgical decompression. Results CTS occurred in 53.3% of HNPP and 11.5% of CMT1A, while CuTS was present in 43.3% of HNPP and 5.8% of CMT1A patients. CTS decompression occurred in 10‐HNPP and 5‐CMT1A patients, and CuTS decompression with/without transposition was performed in 5‐HNPP and 1‐CMT1A patients. In HNPP, electrodiagnostic studies identified median neuropathy at the wrist in 9/10 patients and ultrasound showed focal enlargements at the carpal and cubital tunnels. In CMT1A, median and ulnar sensory responses were all absent, and the nerves were diffusely enlarged. After CTS surgery, pain, sensory loss, and strength improved in 4/5 CMT1A, and 6/10 HNPP patients. Of clinical, electrophysiologic and ultrasound findings, only activity‐provoked features significantly correlated with CTS surgical benefit in HNPP patients (odds ratio = 117.0:95% confidence interval, 1.94 > 999.99, p = 0.01). One CMT1A and one HNPP patient improved with CuTS surgery while 2 HNPP patients worsened. Discussion CTS symptom improvement post‐surgery can be seen in CMT1A and (less frequent) in HNPP patients. CuTS surgery commonly worsened course in HNPP. Activity‐provoked symptoms in HNPP best informed benefits from CTS surgery.

Purpose of review This review aims to summarize the current literature describing vestibular-autonomic interactions and to describe their putative role in various disorders’ clinical presentations, including orthostatic dizziness and motion sensitivity. Recent findings The vestibular-autonomic reflexes have long been described as they relate to cardiovascular and respiratory function. Although orthostatic dizziness may be in part related to impaired vestibulo-sympathetic reflex (orthostatic hypotension), there are various conditions that may present similarly. A recent clinical classification aims to improve identification of individuals with hemodynamic orthostatic dizziness so that appropriate recommendations and management can be efficiently addressed. Researchers continue to improve understanding of the underlying vestibular-autonomic reflexes with recent studies noting the insular cortex as a cortical site for vestibular sensation and autonomic integration and modulation. Work has further expanded our understanding of the clinical presentation of abnormal vestibular-autonomic interactions that may occur in various conditions, such as aging, peripheral vestibular hypofunction, traumatic brain injury, and motion sensitivity. Summary The vestibular-autonomic reflexes affect various sympathetic and parasympathetic functions. Understanding these relationships will provide improved identification of underlying etiology and drive improved patient management.

Abstract Electrical stimulation of the cerebral cortex (ESCC) has been used to treat intractable neuropathic pain for nearly two decades, however, no standardized approach for this technique has been developed. In order to optimize targeting and validate the effect of ESCC before placing the permanent grid, we introduced initial assessment with trial stimulation, using a temporary grid of subdural electrodes. In this retrospective study we evaluate the role of electrode location on cerebral cortex in control of neuropathic pain and the role of trial stimulation in target-optimization for ESCC. Location of the temporary grid electrodes and location of permanent electrodes were evaluated in correlation with the long-term efficacy of ESCC. The results of this study demonstrate that the long-term effect of subdural pre-motor cortex stimulation is at least the same or higher compare to effect of subdural motor or combined pre-motor and motor cortex stimulation. These results also demonstrate that the initial trial stimulation helps to optimize permanent electrode positions in relation to the optimal functional target that is critical in cases when brain shift is expected. Proposed methodology and novel results open a new direction for development of neuromodulation techniques to control chronic neuropathic pain.

AbstractAutonomic neuropathies represent a complex group of disorders that preferentially target autonomic fibers and can be classified as either acute/subacute or chronic in onset. Acute‐onset autonomic neuropathies manifest with such conditions as paraneoplastic syndromes, Guillain‐Barre syndrome, Sjögren syndrome, infection, or toxins/chemotherapy. When the presentation is acute, immune‐mediated, and without a secondary cause, autoimmune autonomic ganglionopathy is likely, and should be considered for immunotherapy. Of the chronic‐onset forms, diabetes is the most widespread and disabling, with autonomic impairment portending increased mortality and cardiac wall remodeling risk. Acquired light chain (AL) and transthyretin (TTR) amyloidosis represent two other key etiologies, with TTR amyloidosis now amenable to newly‐approved gene‐modifying therapies. The COMPASS‐31 questionnaire is a validated outcome measure that can be used to monitor autonomic severity and track treatment response. Symptomatic treatments targeting orthostatic hypotension, among other symptoms, should be individualized and complement disease‐modifying therapy, when possible.

Abstract Background Multiple system atrophy (MSA) is a neurodegenerative disorder from α‐synuclein aggregation. in vitro studies suggest vitamin B12 may interrupt α‐synuclein‐mediated neurodegeneration. The objective of this study was to determine whether serum vitamin B12 level at MSA diagnosis is associated with survival. Methods One hundred eighty‐two MSA patients evaluated at Mayo Clinic with vitamin B12 testing were studied. We determined the risk of death in relationship to serum vitamin B12 levels at MSA diagnosis, adjusting for predictors of poor survival. Results Predictors of shorter survival included vitamin B12 < 367 ng/L (HR, 1.8; 95% CI, 1.3–2.7), falls within 3 years of MSA diagnosis (HR, 1.6; 95% CI, 1.1–2.3), bladder symptoms (HR, 1.6; 95% CI, 1.0–2.6), urinary catheter requirement (HR, 1.7; 95% CI, 1.0–2.8), male sex (HR, 1.4; 95% CI, 1.0–2.0), and MSA‐P subtype (HR, 1.5; 95% CI, 1.0–2.0). Conclusions Low vitamin B12 levels are associated with shorter survival in MSA. Additional studies to explore this observation and assess the potential role of vitamin B12 as a modifiable survival factor are needed. © 2020 International Parkinson and Movement Disorder Society

Abstract The tolerability of long-term posaconazole use remains poorly defined. We present a patient who developed peripheral neuropathy following long-term exposure to the tablet formulation of posaconazole, which was treated with methylprednisolone and magnesium infusions. The potential role of methylprednisolone and magnesium infusions in managing this potentially irreversible triazole-associated complication requires further study.