Epileptic Seizure as a Presenting Symptom of Cerebrotendinous Xanthomatosis

Cerebrotendinous xanthomatosis (CTX) is a rare hereditary disease characterized by xanthomata of tendons, osteoporosis, cataracts, cerebellar ataxia, spastic paresis, and dementia. Though electroencephalographic (EEG) abnormalities are frequent in CTX, epileptic seizures have not been recognized as a major feature. A CTX patient is reported who presented with a generalized epileptic seizure and was evaluated with EEG and neuropsychological testing. Epilepsy should be considered a feature of CTX, and CTX considered as a possible, though rare, cause of symptomatic seizures.     

Cerebrotendinous xanthomatosis: 11-year treatment with chenodeoxycholic acid in five patients. An electrophysiological study

We report the electrophysiological follow-up of five cerebrotendinous xanthomatosis patients treated for 11 years with chenodeoxycholic acid (CDCA). Nerve conduction velocity (NCV) was reduced in three cases. P100 latency of visual evoked potentials was delayed in four cases, interpeaks I–III and I–V of brainstem auditory evoked potentials (BAEPs) was increased in two and interpeak N13–20 of upper limb somatosensory evoked potentials (SEPs) was slowed in one. After 4 months of therapy with CDCA, NCV was normal and did not show any significant change during the 11 years of observation. Central motor conduction time of motor evoked potentials (MEPs) and N24–P40 interpeak latency of lower limb SEPs were increased in five and four cases, respectively, in spite of 2/3-year treatment with CDCA. Improvement of evoked potentials, especially of MEPs and SEPs, was slower and continued over the whole 11-year period. The size of xanthomas slightly decreased in some patients during treatment and the clinical manifestations stabilized, avoiding progressive worsening, but there was no significant improvement in neurological deficit. Two sisters of patients who never took CDCA showed progressive worsening of clinical manifestations, upper limb SEPs and BAEPs.     

New Keys to Early Diagnosis: Muscle Echogenicity,Nerve Ultrasound Patterns,Electrodiagnostic, and Clinical Parameters in 150 Patients with Hereditary Polyneuropathies

Hereditary neuropathies are of variable genotype and phenotype. With upcoming therapies, there is urgent need for early disease recognition and outcome measures. High-resolution nerve and muscle ultrasound is a dynamic, non-invasive, well-established tool in the field of inflammatory and traumatic neuropathies. In this study, we defined nerve and muscle ultrasound parameters as recognition and progression markers in 150 patients with genetically confirmed hereditary neuropathies, including Charcot-Marie-Tooth (CMT) disease (CMT1A, n = 55; other CMT1/4, n = 28; axonal CMT, n = 15; CMTX, n = 15), hereditary neuropathy with liability to pressure palsies (HNPP, n = 16), hereditary transthyretin-amyloidosis (ATTRv, n = 14), and Fabry’s disease (n = 7). The CMT1A, followed by the CMT1/4 group, had the most homogeneous enlargement of the nerve cross-sectional areas (CSA) in the ultrasound pattern sum (UPSS) and homogeneity score. Entrapment scores were highest in HNPP, ATTRv amyloidosis, and Fabry’s disease patients. In demyelinating neuropathies, the CSA correlated inversely with nerve conduction studies. The muscle echo intensity was significantly highest in the clinically most affected muscles, which was independent from the underlying disease cause and correlated with muscle strength and disease duration. Further correlations were seen with combined clinical (CMTES-2) and electrophysiological (CMTNS-2) scores of disease severity. We conclude that nerve ultrasound is a helpful tool to distinguish different types of hereditary neuropathies by pattern recognition, whereas muscle ultrasound is an objective parameter for disease severity. The implementation of neuromuscular ultrasound might enrich diagnostic procedures both in clinical routines and research.Supplementary InformationThe online version contains supplementary material available at 10.1007/s13311-021-01141-3.     

Nerve ultrasound normal values – Readjustment of the ultrasound pattern sum score UPSS

Objective

Reference values are crucial for nerve ultrasound. Here, we reevaluated normal nerve and fascicle cross-sectional area (CSA) values in humans and compared them to published values. Based on these data, ultrasound pattern sum score (UPSS) boundary values were revisited and readjusted.

Cerebrotendinous xanthomatosis: clinical,electrophysiological and nerve biopsy findings,and response to treatment with chenodeoxycholic acid

Summary A 30-year-old patient with cerebrotendinous xanothomatosis was studied over a 6-year period. The clinical manifestations were cataracts, intellectual deterioration, ataxia, palatal and pharyngeal myoclonus, corticospinal tract damage and an electrophysiologically demonstrated sensorimotor peripheral neuropathy. Peripheral motor and sensory nerve conduction velocity was slowed. Sural nerve biopsy revealed reduced densities of both myelinated and unmyelinated axons and teased fibres showed evidence of axonal regeneration and some remyelination. The loss of myelinated nerve fibres particularly affected those of larger diameter, thus contributing to the slowing of nerve conduction. Chenodeoxycholic acid treatment for two separate periods of 10 and 6 months each increased nerve conduction velocity. This electrophysiological improvement was not matched by detectable clinical neurological improvement.     

Patterns and parameters describing nerve thickening in compression and entrapment ulnar neuropathies at the elbow

ObjectiveTo compare pattern and parameters describing nerve thickening in ulnar neuropathy at the elbow (UNE) due to external compression in the retrocondylar groove (RTC), and entrapment under the humeroulnar aponeurosis (HUA).MethodsIn a group of our previously reported UNE patients we ultrasonographically (US) measured ulnar nerve cross-sectional areas (CSA) on 6–8 standard locations in the elbow segment. We compared CSA patterns in both groups, and determined diagnostic utility of selected CSA based parameters.ResultsWe studied 79 patients (81 arms) with UNE due to external compression, and 53 patients (55 arms) due to entrapment. Maximal ulnar nerve CSA (>16 mm²), maximal CSA change (>7 mm²/1–2 cm) and maximal/minimal CSA ratio (>2.6) were significantly larger in UNE due to entrapment. They also differentiated these arms from arms with compression with sensitivities of 78%, 87% and 80%, and specificities of 90%, 94%, and 85%, respectively.ConclusionMaximal difference in CSA between points separated by 1–2 cm (>7 mm²/1–2 cm) very efficiently differentiated between UNE due to external compression and entrapment.SignificanceThe proposed parameter will hopefully complement precise localization in determining underlying mechanism of UNE. This may help physicians to determine the most appropriate treatment for UNE and possibly other focal neuropathies of unknown cause; i.e., conservative treatment for external compression and surgery for entrapment.     

Haemodialysis alters peripheral nerve morphology in end-stage kidney disease

Objective

We explored the nerve ultrasound (US) characteristics of 15 patients with end-stage kidney disease (ESKD) and correlated these findings with clinical severity and electrophysiological parameters of neuropathy.

高频超声、神经电生理对糖尿病性周围神经病的手术评估

目的 探讨高频超声、神经电生理在糖尿病性周围神经病(DPN)早期诊断及其神经减压手术时机、疗效评估中的应用价值.方法 对560例糖尿病性下肢周围神经病患者,按Dellon术式对卡压神经进行显微松解术.所有病例术前、术后1.5年进行多伦多临床神经病变评分(TCSS),神经高频超声、定量感觉功能(QST)、神经感觉传导速度(NCV)检测,并在相应时间节点采用同样指标与健康对照组进行对比.结果 DPN患者高频超声显示受累神经肿胀、增粗,内部回声减低,神经内线状结构消失,神经前后径(D1)和横径(D2),横断面积(CSA)手术前后差异有统计学意义(P＜0.01).NCV阳性检测率为74.9%,QST阳性检测率为90.9%,两者差异有统计学意义.DPN早期诊断QST较NCV更为敏感.NCV术后较术前明显增快(P＜0.05),冷感觉阈值较术前明显升高(P＜0.05);热感觉阈值较术前明显降低(P＜0.01);振动觉阈值较术前明显降低(P＜0.05).NCV与冷感觉阈值呈正相关;与热感觉阈值、振动觉阈值呈负相关.术前TCSS评分19分者术后75%改善至10～13分(P＜0.01).结论 高频超声能够从形态学角度提供神经卡压程度、部位等信息.QST检测适用于DPN的早期诊断,QST异常是实施下肢神经减压术的适应证.QST与NCV两者联合使用对把握手术时机具有重要意义,高频超声、NCV、QST可作为评价手术疗效的客观依据.     

Multifocal motor neuropathy: correlation of nerve ultrasound,electrophysiological, and clinical findings

We present nerve ultrasound findings in multifocal motor neuropathy (MMN) and examine their correlation with electrophysiology and functional disability. Eighty healthy controls and 12 MMN patients underwent clinical, sonographic, and electrophysiological evaluation a mean of 3.5 years (standard deviation [SD] ± 2.1) after disease onset. Nerve ultrasound revealed significantly higher cross‐sectional area (CSA) values of the median (forearm, p < 0.001), ulnar (p < 0.001), and tibial nerve (ankle, p < 0.001) when compared with controls. Electroneurography documented signs of significantly lower values of the motor conduction velocity and compound muscle action potentials (cMAPs) in the upper arm nerves (median, ulnar, radial, p < 0.001). A significant correlation between sonographic and electrophysiological findings in the MMN group was found only between cMAP and CSA of the median nerve at the upper arm (r = 0.851, p < 0.001). Neither nerve sonography nor electrophysiology correlated with functional disability. MMN seems to show inhomogeneous CSA enlargement in various peripheral nerves, with weak correlation to electrophysiological findings. Neither nerve sonography nor electrophysiology correlated with functional disability. Multicentre, prospective studies are required to prove the applicability and diagnostic values of these findings.     

Utility of nerve conduction studies and ultrasonography in ulnar neuropathies at the elbow of different severity

ObjectiveTo report the sensitivity and the ability to precisely localize ulnar neuropathies at the elbow (UNE) of different severity by ultrasonography (US) and compare it to standard 10-cm nerve conduction studies (NCSs), and 2-cm short-segment NCSs (SSNCSs) across the elbow.MethodsIn a group of consecutive UNE patients, a prospective and blinded study was performed. The evaluation included clinical examination, electrodiagnostic (EDx) and US studies. We compared US and NCSs for sensitivity and the ability to precisely localize the UNE of different clinical severity.ResultsWe studied 202 affected arms of 197 UNE patients. Clinically very mild UNE was diagnosed in seven, mild in 43, moderate in 99 and severe in 53 arms. The sensitivities of SSNCSs were 14%, 67%, 93% and 100%, of 10-cm NCSs, 29%, 44%, 80% and 96%, and of US 14%, 47%, 59% and 89%, respectively. Precise UNE localization was possible using SSNCSs in 29%, 56%, 78% and 85%, and using US in 29%, 44%, 70% and 98%, respectively.ConclusionThe present study demonstrated that NCSs are more sensitive than US for the diagnosis of UNE of all clinical grades of severity. US was more efficient in localizing clinically severe, and SSNCSs in localizing mild or moderate UNE.SignificanceWe recommend SSNCSs as the first confirmatory test in UNE across all grades of severity.     

糖尿病病程对糖尿病下肢周围神经病变的影响

目的探讨糖尿病（DM）病程对糖尿病周围神经病变（DPN）严重程度及下肢周围神经显微减压术疗效的影响,以及糖尿病周围神经病变早期诊断、早期手术的意义。方法以5年糖尿病痛程作为标准,将我科近年收治的1526例糖尿痛周围神经病患者分为短DM病程组和长DM病程组,按Dellon术式对卡压的神经进行下肢周围神经显微减压术。所有患者术前、术后1.5年进行神经高频超声、定量感觉检查（QST）、神经感觉传导速度（NCV）检测,并选取50例正常人群作为对照组检测相同指标。结果与对照组相比,DPN患者的NCV、冷感觉阈值较低,热感觉阈值、振动觉阈值及神经横断面积（CSA）较高,差异有统计学意义（P〈0．05）。患者术后各项指标明显改善,与术前相比,差异有统计学意义（P〈0．05）。短DM病程DPN患者术前和术后各指标均优于长DM病程DPN患者,两组比较差异有统计学意义（P〈0．05）。短DM病程DPN患者NCV阳性检测率为71．5％,QST阳性检测率为93．7％;长DM病程DPN患者NCV阳性检测率为90．3％,QST阳性检测率为95．3％。结论糖尿病痛程对DPN患者发病时的严重程度至关重要,同时也对DPN患者的手术疗效和预后产生影响。DPN的早期诊断、早期手术具有重要临床价值。     

The neurocytokine, interleukin-6, corrects nerve dysfunction in experimental diabetes

Interleukin-6 (IL-6) is a member of the neuropoietic cytokine family and has a multifunctional biological role in regulating the immune response, acute phase reactions, and hematopoiesis. IL-6 is also important in neural development and has neurotrophic actions. The aim was to ascertain whether IL-6 treatment could rectify some of the adverse early changes in neurovascular function in streptozotocin-induced diabetic rats. After 4 weeks of untreated diabetes, rats were treated with IL-6 (1-10 microg/kg thrice weekly) for 4 weeks. Diabetes caused 22% and 22.5% reductions in sciatic nerve motor and saphenous nerve sensory conduction velocity, respectively, which were dose dependently corrected by treatment. Diabetic rats also showed thermal hyperalgesia and tactile allodynia, which were completely corrected by IL-6; however, IL-6 was ineffective against mechanical hyperalgesia. Sciatic nerve endoneurial perfusion was 42.2% reduced by diabetes and blood flow was returned to the nondiabetic range by 10 microg/kg IL-6 treatment. The ED(50) values for these actions ranged from 1.2 microg/kg for sensory conduction velocity to 3.2 microg/kg for sciatic nerve perfusion. Thus, IL-6 treatment improved several measures of nerve dysfunction in experimental diabetes, and these effects correlated with a recovery of nerve blood flow. The magnitude of these beneficial effects and the potential joint neurotrophic and vascular action suggests that IL-6 could be a candidate for further evaluation in clinical trials of diabetic neuropathy.     

Quantitation of the Schmidt-Lanterman incisures in juvenile,adult, remyelinated and regenerated fibres of the chicken sciatic nerve

Summary Morphometric studies of peripheral nerves in various species have shown that the number of Schmidt-Lanterman incisures in an internode is proportional to the fibre diameter. In the rat sural nerve it appears that following remyelination, the relationship between the numbers of incisures per internode and the fibre diameter remains unaltered despite the fact that the remyelinated internodes are uniformly short.We quantitatively examined the insertion of incisures in adult, juvenile, remyelinated and regenerated fibres of the chicken sciatic nerve. Remyelinated fibres were examined 100 and 200 days following the intraneural injection of diphtheria toxin, and regenerated fibres 200 days after a nerve crush. Our results show that the incisures are more abundant in the chicken than in all other species previously reported, and for both juvenile and adult hens the number of incisures in an internode is proportional to the fibre diameter.Following both remyelination and regeneration the internodal lengths were shorter than control fibres and the distances between the incisures were reduced by approximately 20% for all fibre diameters. Significantly, the numbers of incisures in an internode were related to the length of the remyelinated or regenerated internode and not to the fibre diameter. This finding is in marked contrast to previous reports for rat peripheral nerve.Our findings are discussed in relation to the hypothesis that the Schmidt-Lanterman incisures are vital to the maintenance of the myelin sheath and/or the associated axon.     

The nerve sheath tumor,solitary and in von Recklinghausen's disease; A unitary mesenchymal concept

Summary The characteristic cell of peripheral nerves, the Schwann cell, is capable of forming peripheral myelin, but also of forming collagen and reticulin fibers and of being transformed into macrophages. This kind of cell has been demonstrated under circumstances in which its formation from pre-existing Schwann cells is precluded, as in regenerative foci within the brain in multiple sclerosis. It is suggested that this cell is a specilized mesenchymal element, and that it may be formed by maturation of the multipotential primitive reticular cells which give rise to other specialized mesenchymal elements in appropriate circumstances, and which are present in the brain as well as in most other tissues.It is suggested that only one type of neoplasm of specific Schwann cell origin exists, this being the same in the presence or absence of von Recklingshausen's neurofibromatosis. It may most simply be designated as the nerve sheath tumor. Von Recklinghausen's disease, however, is characterized by the occurrence of hamartomatous and degenerative phenomena, as well as the tendency to neoplasia, and these alter the appearnce of the specific nerve sheath tumor and of non-neoplastic segments of peripheral nerves. In addition, some neoplasms observed in this disease have been interpreted as of Schwann cell origin when, in fact, they are less specific fibromas originating in other connective tissue elements of a nerve, or in the extra-neural connective tissues. The term neurofibroma appears to have been applied to both of these phenomena, i.e., to degenerative, non-neoplastic changes in nerves, and to neoplasms which may not have originated in Schwann cells or even within peripheral nerves; its continued use is not warranted.

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Zusammenfassung Die für den peripheren Nerven kennzeichnende Zelle, die Schwannsche Zelle, ist imstande, sowohl Myelin vom peripheren Typ als auch Kollagen und Reticulin zu produzieren und als Makrophage tätig zu sein. Diese Fähigkeit der Zelle konnte unter solchen Umständen beobachtet werden, unter denen ihre Bildung aus autochthonen Schwannschen Zellen zwingend ausgenommen werden mußte, wie z.B. in den Foci der multiplen Sklerose im Gehirn. Es wird die Annahme vorgebracht, daß diese Zelle ein besonderes bindegewebiges Element ist, das sich durch Reifung von den multipotenten primitiven Reticulumzellen ableitet, die unter bestimmten Umständen auch andere spezielle mesenchymale Elemente produzieren, und die im Gehirn wie in den meisten anderen Geweben vorhanden sind.Ferner wird postuliert, daß es nur eine einzige Art von Geschwülsten der Schwannschen Zelle gibt, ungeachtet dessen, ob die von Recklinghausensche Neurofibromatose vorliegt oder nicht. Diese Geschwulst sollte einfach als Nervenscheidentumor bezeichnet werden. Die Recklinghausensche Krankheit ist jedoch durch das Vorkommen von Hamartomen und degenerativen Phänomenen sowie durch eine Bereitschaft zur Geschwulstbildung gekennzeichnet. Diese Momente ändern das Bild eines spezifischen Nervenscheidetumors sowie das der nichtneoplastischen Segmente des peripheren Nerven. Einige Geschwülste, die bei dieser Erkrankung vorkommen, wurden als Derivate der Schwannschen Zellreihe angesehen, während sie in Wirklichkeit weniger spezifische Fibrome sind, die ihren Ursprung von anderen Bindegewebselementen des Nerven oder des extraneuralen Gewebes nehmen. Die Bezeichnung Neurofibrom hat man anscheinend auf beide dieser Phänomene angewandt, d.h. auf Fälle, von regressiven, nicht-neoplastischen Veränderungen der Nerven und auf solche Geschwülste, die ihren Ursprung möglicherweise weder von der Schwannschen Zelle noch überhaupt im peripheren Nerven genommen hatten. Die weitere Anwendung dieser Bezeichnung erscheint unberechtigt.

     

Comparison of electrodiagnosis,neurosonography and MR neurography in localization of ulnar neuropathy at the elbow

IntroductionIn patients with ulnar neuropathy at the elbow (UNE) the precise determination of the site of lesion is important for subsequent differential diagnostic considerations and therapeutic management. Due to a paucity of comparable data, to better define the role of different diagnostic tests, we performed the first prospective study comparing the diagnostic accuracy of short segment nerve stimulation, nerve ultrasonography, MR neurography (MRN), and diffusion tensor imaging (DTI) in patients with UNE.MethodsUNE was clinically diagnosed in 17 patients with 18 affected elbows. For all 18 affected elbows in patients and 20 elbows in 10 healthy volunteers, measurements of all different diagnostic tests were performed at six anatomical positions across the elbow with measuring points from distal (D4) to proximal (P6) in relation to the medial epicondyle (P0). Additional qualitative assessment regarding structural changes of surrounding nerve anatomy was conducted.ResultsThe difference between affected arms of patients and healthy control arms were most frequently the largest at measure intervals D2 to P0 and P0 to P2 for electrophysiological testing, or measure points P0 and P2 for all other devices, respectively. At both levels P0 and at P2, T2 contrast-to-noise ratio (CNR) of MRN and mean diffusivity (MD) of DTI-based MRN showed best accuracies.DiscussionThis study revealed differences in diagnostic performance of tests concerning a specific location of UNE, with better results for T2 contrast to noise ratio (CNR) in MRN and mean diffusivity of DTI-based MRN. Additional testing with MRN and nerve ultrasonography is recommended to uncover anatomical changes.     

Evaluation of fosphenytoin,levetiracetam, and propofol as treatments for nerve agent-induced seizures in pediatric and adult rats

Multiple recent instances of nerve agent (NA) exposure in civilian populations have occurred, resulting in a variety of negative effects and lethality in both adult and pediatric populations. Seizures are a prominent effect of NAs that can result in neurological damage and contribute to their lethality. Current anticonvulsant treatments for NAs are approved for adults, but no approved pediatric treatments exist. Further, the vast majority of NA-related research in animals has been conducted in adult male subjects. There is a need for research that includes female and pediatric populations in testing. In this project, adult and pediatric male and female rats were challenged with sarin or VX and then treated with fosphenytoin, levetiracetam, or propofol. In this study, fosphenytoin and levetiracetam failed to terminate seizure activity when animals were treated 5 min after seizure onset. Propofol was effective, exhibiting high efficacy and potency for terminating seizure activity quickly in pediatric and adult animals, suggesting it may be an effective anticonvulsant for NA-induced seizures in pediatric populations.