Brian A. Crum

Treatment of a Segmental Nerve Defect in the Rat with Use of Bioabsorbable Synthetic Nerve Conduits: A Comparison of Commercially Available Conduits

BACKGROUND The use of biodegradable synthetic nerve conduits for the reconstruction of segmental nerve defects has been extensively reported in both animal and human studies, with a majority of studies evaluating sensory nerve recovery. However, few studies have compared these nerve conduits for functional motor recovery. The purpose of this study was to compare three commercially available, synthetic, bioabsorbable nerve conduits and autograft with respect to compound muscle action potentials, maximum isometric tetanic force, wet muscle weight, and nerve histomorphometry. METHODS Eighty Lewis rats were divided into four groups according to the type of repair of a 10-mm excision of the sciatic nerve: group I had a reversed autograft; group II, a poly-DL-lactide-epsilon-caprolactone conduit; group III, a type-I collagen conduit; and group IV, a polyglycolic acid conduit. All results were compared with the contralateral side. At twelve weeks, the rats underwent bilateral measurements of the compound muscle action potentials of the tibialis anterior and flexor digiti quinti brevis muscles, isometric tetanic force and muscle weight of the tibialis anterior, and peroneal nerve histomorphometry. RESULTS At twelve weeks, no difference in the percentage of recovery between the autograft and the poly-DL-lactide-epsilon-caprolactone conduit was observed with respect to compound muscle action potentials, isometric muscle force, muscle weight, and axon count measurements. The poly-DL-lactide-epsilon-caprolactone and collagen conduits remained structurally stable at twelve weeks, while the polyglycolic acid conduits had completely collapsed. The polyglycolic acid conduit had the poorest results, with a recovery rate of 15% for compound muscle action potentials and 29% for muscle force. CONCLUSIONS The functional outcome in this rat model was similar for the autograft and the poly-DL-lactide-epsilon-caprolactone conduits when they were used to reconstruct a 10-mm sciatic nerve defect. Functional recovery following the use of the polyglycolic acid conduit was the poorest.

Linezolid-Associated Peripheral Neuropathy

Linezolid is the first drug in a new class of synthetic antimicrobials, the oxazolidinones, to be approved by the Food and Drug Administration. Linezolid is active against methicillin- and vancomycin-resistant gram-positive microorganisms. We describe 2 patients who developed peripheral neuropathy after prolonged treatment with linezolid. Linezolid-associated peripheral neuropathy has not been well documented. Most reported cases of linezolid-associated peripheral neuropathy have occurred in patients who took linezolid for a period longer than the recommended 28 or fewer days. Health care providers must be alert to the potential for serious adverse effects associated with linezolid use, including peripheral neuropathy.

Caffeine for the prevention and treatment of postdural puncture headache: debunking the myth.

Objective:Is caffeine effective in preventing and treating postdural puncture headache (PDPH)? Methods:The question was addressed with a structured evidence-based clinical neurologic practice review via videoconferencing between 3 academic institutions. Participants included consultant and resident neurologists, clinical epidemiologists, medical librarians, and clinical content experts. A critically appraised topic format was employed, starting with a clinical scenario and structured question. Participant groups at each of the 3 institutions independently devised search strategies, located and compiled the best evidence, performed critical appraisals, synthesized the results, summarized the evidence, provided commentary, and declared bottom-line conclusions. Results:Three directly relevant randomized controlled trial articles were selected as the best available evidence for the clinical questions. Two investigated caffeine [oral and intravenous (IV)] as PDPH prophylaxis and 1 (oral) as PDPH treatment. One additional quasirandomized trial (IV) and 1 open-label trial (IV) of caffeine for PDPH treatment were located by reviewing bibliographies. Articles describing the pharmacological basis for caffeine therapy were also identified. No valid pharmacological rationale for caffeine as an antinociceptive agent for PDPH exists. The clinical trials are few in number, small in sample size, methodologically weak or flawed, and either demonstrate no effectiveness, contradictory and conflicting results, or invalid answers. Conclusions:The wide endorsement for caffeine to prevent and treat PDPH found in textbooks and review articles appears to be unwarranted and insufficiently supported by the available pharmacological and clinical evidence.

Basal ganglia T1 hyperintensity in LGI1-autoantibody faciobrachial dystonic seizures.

Objective: To characterize the clinical features and MRI abnormalities of leucine-rich glioma-inactivated 1 (LGI1)-autoantibody (Ab) faciobrachial dystonic seizures (FBDS). Methods: Forty-eight patients with LGI1-Ab encephalopathy were retrospectively identified by searching our clinical and serologic database from January 1, 2002, to June 1, 2015. Of these, 26 met inclusion criteria for this case series: LGI1-Ab seropositivity and FBDS. In a separate analysis of all 48 patients initially identified, the MRIs of patients with (n = 26) and without (n = 22) FBDS were compared by 2 neuroradiologists blinded to the clinical details. Results: The median age of the 26 included patients was 62.5 years (range 37–78); 65% were men. FBDS involved arm (26), face (22), and leg (12). Ten were previously diagnosed as psychogenic. Ictal EEGs were normal in 20 of 23 assessed. Basal ganglia T1 and T2 signal abnormalities were detected in 11 patients (42%), with excellent agreement between neuroradiologists (κ scores of 0.86 and 0.93, respectively), and included T1 hyperintensity alone (2), T2 hyperintensity alone (1), or both (8). The T1 hyperintensities persisted longer than the T2 hyperintensities (median 11 weeks vs 1 week, p = 0.02). Improvement with immunotherapy (18/18) was more frequent than with antiepileptic medications (10/24). A separate analysis of all 48 patients initially identified with LGI1-Ab encephalopathy showed that basal ganglia MRI abnormalities were present in 11 of 26 with FBDS but not present in those without FBDS (0/22) (p < 0.001). In contrast, mesial temporal MRI abnormalities were less common among those with FBDS (42%) than those without (91%) (p < 0.001). Conclusions: Basal ganglia T1 hyperintensity is a clinically useful MRI biomarker of LGI1-Ab FBDS and suggests a basal ganglia localization.

EFFECT OF REFERRAL BIAS ON ASSESSING SURVIVAL IN ALS

We assessed the effect of referral bias on patients with ALS treated at our medical center. A total of 132 subjects were treated by our center over the past 3 years. The referral population had a median survival of 29 months compared to 18 months for the local population (p = 0.007). Referral bias should be addressed when assessing the efficacy of self-selected therapies in the setting of a tertiary ALS clinic.

Venous congestive myelopathy: a mimic of neoplasia

Venous congestive myelopathy is a progressive disorder frequently associated with arteriovenous fistulas, usually dural. By causing diffuse spinal cord enlargement and enhancement on imaging, it may simulate a neoplasm and prompt a biopsy. We evaluated the biopsy findings in seven such patients (M=5, F=2, mean age 59±11 years) who presented variably with progressive lower extremity weakness (86%), bowel and bladder dysfunction (86%), sensory changes (86%) or pain (29%). Preoperative magnetic resonance imaging showed spinal cord enlargement with T2-hyperintensity (86%) and contrast enhancement (57%) at the cervical (14%), thoracolumbar (57%), and/or conus medullaris (57%) level. Prebiopsy spinal angiogram, performed in two patients, was negative. Spinal cord biopsy showed architecturally distorted parenchyma with gliosis and thick hyalinized vessels (100%), variable myelin loss (71%), mild glial atypia (57%), hemosiderin deposition (71%), Rosenthal fibers (43%), vascular thrombosis (29%), and necrosis (29%), features highly suggestive of venous congestive myelopathy. Postbiopsy spinal angiograms were performed in five patients. A dural arteriovenous fistula was identified by selective angiography in three patients, including the two with a negative preoperative angiogram. Additional postbiopsy angiographic studies in two patients were negative, and two patients were followed up without angiography. Mean follow-up after biopsy was 13.6 months. Histologic changes characteristic of venous congestive myelopathy may be seen in spinal cord biopsies with or without an associated fistula. Recognition of this entity by surgical pathologists is important, leading to the correct identification of a non-neoplastic lesion as well as of a surgically treatable disease.

Alpha-lipoic acid may improve symptomatic diabetic polyneuropathy.

Objective:In patients with symptomatic diabetic polyneuropathy, is oral alpha-lipoic acid (ALA) effective in improving neuropathic symptoms compared with placebo? Methods:The question was addressed with a structured evidence-based clinical neurologic practice review via videoconferencing between 3 academic institutions. Participants included consultant and resident neurologists, clinical epidemiologists, medical librarians, and clinical content experts. A critically appraised topic format was employed, with a clinical scenario, structured question, search strategy, appraisal, results, summary of evidence, commentary, and bottom-line conclusions. Results:A single modestly valid randomized controlled trial demonstrated that oral ALA in doses of 600 mg, 1200 mg, and 1800 mg was effective in reducing neuropathic symptoms of diabetic distal symmetric polyneuropathy (DSP) at 5 weeks, as assessed by the Total Symptom Score (≥50% reduction), with number needed to treat (NNT) (95% CI) of 2.7 (1.8 to 5.8), 4.1 (2.3 to 20.2), and 3.2 (2.0 to 8.6), respectively. Adverse events, including nausea, vomiting, and vertigo, were identified but occurred most frequently with ALA doses of 1200 mg and 1800 mg. Overall, treatment emergent adverse events for ALA 600 mg were not significantly different than placebo, but ALA 1200 mg and 1800 mg had number needed to harm (95% CI) of 4.5 (2.4 to 31.0) and 3.0 (1.9 to 7.1), respectively. Conclusion:Oral ALA may improve neuropathic symptoms in diabetic DSP. A single modestly valid RCT demonstrated that 600 mg was an effective and well-tolerated dose, with NNT 2.7 to significantly reduce neuropathic pain symptoms over a 5-week period. ALAs role and place in an algorithm among other commonly prescribed oral treatments for symptomatic relief of neuropathic pain in diabetic DSP remains unclear.

Fulminant case of hereditary neuropathy with liability to pressure palsy

Hereditary neuropathy with liability to pressure palsy (HNPP) is typified as isolated nerve palsies caused by trivial compression or trauma. It rarely presents in two extremities and even more infrequently affects all four limbs simultaneously. We present a patient who concurrently experienced right shoulder, left hand, and bilateral foot weakness mimicking several multifocal conditions. Electromyography suggested HNPP and subsequent nerve biopsy and genetic testing were confirmatory. The case demonstrates that HNPP can present in a fulminant manner and should be included in the differential diagnosis of acute multiple mononeuropathies. The possible causes for such a rapid clinical course in our patient are discussed.

ANO5‐muscular dystrophy: clinical, pathological and molecular findings

Anoctamin 5 (ANO5) is a putative intracellular calcium‐activated chloride channel. Recessive mutations in ANO5 cause primary skeletal muscle disorders (limb‐girdle muscular dystrophy 2L and distal muscular dystrophy), which are phenotypically similar to dysferlinopathy, a muscular dystrophy due to dysferlin‐encoding gene (DYSF) mutations.

Peripheral nerve stimulation and monitoring during operative procedures

Monitoring of peripheral nerve function is important during the surgical treatment of peripheral nerve and plexus lesions, allowing for rapid assessment of the integrity of the roots, plexus, and nerves. The results of this monitoring assist the surgeon in the overall approach to treatment of these lesions. There are, however, many technical challenges to providing this neurophysiological information in an accurate and rapid fashion. This study assesses the equipment and techniques involved in intraoperative peripheral nerve monitoring and describes its use in the more common clinical scenarios. Muscle Nerve, 2006