Neurographic course Of Wallerian degeneration after human peripheral nerve injury.

INTRODUCTION: Neurographic data on Wallerian degeneration (WD) after motor nerve injury are available only from animal studies and human case reports of 9 patients altogether. A precise knowledge of neurographic features of WD would be highly relevant for diagnostic, prognostic, therapeutic, and forensic aspects of traumatic lesions. METHODS: We prospectively studied WD in patients with a peripheral nerve injury. They underwent sequential neurographic examinations beginning no later than 3 days after the injury until a plateau of the amplitude of compound muscle action potential was reached. RESULTS: We examined 20 injured nerves from 16 patients. Four days after injury, all nerves showed amplitude decay to some extent, whereas 85% had reached their plateau at day 8. A length dependency of WD could be demonstrated. CONCLUSION: In humans, WD starts no later than day 4, shows length dependency, and is completed at day 8 in most nerves. Muscle Nerve 56: 247-252, 2017.

[Neuralgic amyotrophy: an inflammatory neuropathy and its surgical treatment]. / Neuralgische Amyotrophie ­ eine entzündliche Neuropathie und ihre operative Behandlung.

BACKGROUND: Neuralgic amyotrophy (NA) is a monofocal or oligofocal inflammatory neuropathy whose incidence has been significantly underestimated. A connection between constrictions and torsions of peripheral nerves with this disease has been increasingly established in recent years. Modern imaging techniques such as high-resolution nerve ultrasound and MR neurography have contributed to a better understanding of the pathophysiology and a better assessment of the prognosis of the disease. This has led to the concept of treating patients with such focal changes surgically in order to improve the prognosis. This review presents current ideas on the pathophysiology, clinical presentation, diagnosis and treatment of the disease. PATIENTS AND METHODS: In a retrospective study, pre-, intra- and postoperative findings of 22 patients with 23 constrictions/torsions of peripheral nerves of the upper extremity were analysed. The patients underwent surgery at a nerve surgery centre over a period of 3.5 years (Dec. 2019-May 2023). The median nerve was most frequently affected (N=9), followed by the suprascapular nerve (N=6) and radial nerve (N=4). The axillary nerve (N=3) and the accessory nerve (N=1) were also involved. Surgical exploration revealed nerve torsions (N=9), nerve constrictions (N=5), fascicular torsions (N=12) and fascicular constrictions (N=9). Depending on the intraoperative findings, epineuriotomies (N=1), epi- and perineuriotomies (N=33), end-to-end sutures (N=2), and one epi- and one perineural suture were performed. RESULTS: After an average follow-up of 10 months (3-28 months), 17 patients were re-examined. All of them reported a clear subjective improvement in motor deficits. Clinically and electromyographically, a reinnervation and significant increase in strength from a pre-existing strength grade of M0 to at least M3 in the vast majority of affected muscles was demonstrated in these patients. SUMMARY: The incidence of NA continues to be underestimated and, in a significant proportion of patients, leads to permanent motor deficits, most likely due to constrictions and torsions of affected nerves. Surgical treatment is recommended as early as possible. Very good results can usually be achieved with epi- and perineuriotomy. In rare cases, end-to-end neurorrhaphy or nerve grafting is required.

Early changes on electroencephalography in natalizumab-associated progressive multifocal leucoencephalopathy.

Progressive multifocal leucoencephalopathy has become a growing concern in natalizumab-treated multiple sclerosis patients. Here, we describe a 35-year-old patient who was treated with 34 infusions of natalizumab before complaining about visual deterioration. MRI was non-diagnostic and JC virus testing initially was negative. Electroencephalography showed severe slowing of the right hemisphere, and neuropsychological testing revealed right frontal and temporal deficits. The diagnosis of progressive multifocal leucoencephalopathy was established 2 months later by typical MRI presentation and detection of JC virus DNA in the cerebrospinal fluid. Functional neurological deficits may precede imaging features and should prompt early consideration of progressive multifocal leucoencephalopathy.

Multifocal, hypoechogenic nerve thickening in Cerebrotendinous Xanthomatosis.

OBJECTIVE: To characterize peripheral nerve morphology in cerebrotendinous xanthomatosis (CTX) patients using high-resolution ultrasound (HRUS) in vivo. We hypothesized that nerve enlargements might be present in CTX as a result of accumulation of abnormal lipids with deposition also in peripheral nerves. METHODS: Four CTX patients were examined using HRUS to assess morphological abnormalities of peripheral nerves as well as cervical nerve roots 5 and 6. RESULTS: HRUS revealed mild to moderate, hypoechogenic thickening of sensorimotor nerves (ulnar nerve in 1/4, tibial nerve in 3/4, median nerve 4/4 patients) as well as mild enlargement of pure sensory nerves (sural nerve in 2/3, superficial FN in 2/4 patients). The vagal nerve was moderately enlarged in one patient, cervical roots showed moderate enlargements of C5 in two patients, one of which also showing thickening of C6 as well as in another patient. UPSS score was slightly to moderately abnormal in all patients. The Homogeneity score was not increased suggesting regional to inhomogeneous nerve enlargement. CONCLUSIONS: HRUS shows multifocal, hypoechogenic nerve thickening of peripheral nerves and nerve roots in CTX. SIGNIFICANCE: HRUS might serve as a valuable, additive and non-invasive bedside tool to assess peripheral nerve morphology in future clinical studies on CTX patients.

Autonomic and peripheral nervous system function in acute tick-borne encephalitis.

OBJECTIVES: Tick-borne encephalitis (TBE) is an emerging flaviviral zoonosis in Central and Eastern Europe. TBE can present as meningitis, meningoencephalitis, or meningoencephalomyelitis. Dysfunction of the autonomic (ANS) and peripheral motoric and sensory nervous system (PNS) might contribute to acute and long-term complications. We aimed to examine, whether the ANS and PNS are affected in acute TBE. METHODS: Fourteen patients with acute TBE, 17 with diabetic polyneuropathy (d-PNP), and 30 healthy controls (HC) were examined in our single-center, prospective study. ANS and PNS function was assessed by time- and frequency-domain parameters of the heart rate (HR) variability at rest and deep respiration, and by sural and tibial nerve neurography. Primary endpoint was the HR variability at rest measured by root mean square of the successive differences (RMSSD). Autonomic symptoms and quality of life (QoL) were assessed by questionnaires. RESULTS: Tick-borne encephalitis patients had a lower RMSSD at rest (TBE 13.1 ± 7.0, HC 72.7 ± 48.3; P < 0.001) and deep respiration (TBE 42.8 ± 27.0, HC 109.7 ± 68.8; P < 0.01), an increased low-frequency to high-frequency power component ratio at rest (TBE 4.0 ± 4.0, HC 0.8 ± 0.5; P < 0.001), and a higher minimal heart rate at rest (TBE 85.4 ± 7.0, HC 69.5 ± 8.5; P < 0.001), all similar to patients with d-PNP, indicating sympathovagal imbalance with increased sympathetic activation. Compared to HC, sural and tibial nerve conduction velocities and action potential amplitudes were reduced, ANS symptoms were more frequent, and QoL was lower in patients with TBE. CONCLUSIONS: The ANS and to a lesser degree the PNS are affected by acute TBE, which could potentially contribute to short- and long-term morbidity.

Toll-like receptor triggered dendritic cell maturation and IL-12 secretion are necessary to overcome T-cell inhibition by glioma-associated TGF-beta2.

Malignant gliomas are able to secrete large amounts of immunosuppressive cytokines like transforming growth factor beta 2 (TGF-beta2) and regularly escape from immune surveillance. Many strategies have been developed to induce potent anti-glioma responses, among those the use of dendritic cells (DC) as therapeutic vaccines. Here, we report that both mature DC and IL-12 secretion are necessary to overcome T-cell inhibition by TGF-beta2. Flow cytometric analyses showed that TGF-beta2 does not suppress the upregulation of MHC (major histocompatibility complex) class II molecules and the T cell stimulatory capacity of human DC that were stimulated with a strong cytokine cocktail containing tumor necrosis factor alpha (TNF-alpha), IL-1beta, IL-6 and prostaglandin E2 (PGE2). Moreover, TGF-beta2 signaling studies revealed that these cytokine-matured DC become unresponsive to TGF-beta2. Although both mature and immature DC expressed comparable amounts of the TGF-beta receptor type II, Smad2 phosphorylation and subsequent upregulation of Smad7 was inhibited in mature DC, but not immature DC. However, further analysis revealed that mature DC alone are not sufficient to mediate full T cell activation in the presence of TGF-beta2, unless IL-12 is added to the DC/T-cell coculture. Finally, we demonstrate that MHC class II expression and IL-12 secretion by DC are not disturbed by TGF-beta2 after DC stimulation with a modified maturation cocktail containing the Toll-like receptor (TLR)-ligands Poly I:C or R848, TNF-alpha, IL-1beta and INF-gamma. These data imply that mature DC retaining their capacity to produce IL-12 are of favorable use in glioma immunotherapy and suggest that TLR triggering of DC plays an important role to elicit a strong immune response in the immunosuppressive environment of malignant gliomas.