Peripheral neuropathy in Cockayne syndrome

Two siblings with Cockayne syndrome are reported. In one case a sural nerve biopsy showed a demyelinating peripheral neuropathy with occasional inclusions in Schwann cells made up of electron dense finely granular material intermingled with vacuoles or lamellar structures. The significance, if any, of this accumulated material remains unclear. The presence, in addition, of small finely lamellar intra-axonal osmiophilic bodies suggests an associated axonal involvement

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Sommario Vengono descritti due casi di Sindrome di Cockayne. In un caso è stata effettuata una biopsia del nervo surale che ha evidenziato una neuropatia periferica di tipo demielinizzante con rare inclusioni nelle cellule di Schwann, formate da materiale osmiofilo finemente granulare, vacuoli e strutture lamellari. Il significato di tali inclusioni è molto incerto. La presenza inoltre di corpi osmiofili lamellari intrassonali suggerisce una associata compromissione assonale.

     

Peripheral neuropathy in myotonic dystrophy type 1

Myotonic dystrophy 1 (DM1) is characterized by a wide range of clinical features. We aimed to verify the presence of peripheral nerve involvement in a large cohort of DM1 patients and to determine clinical consequences. A total of 93 patients underwent detailed neurological examination and nerve conduction studies. Additionally, balance impairment was assessed with the Berg Balance Scale and health status was evaluated with the SF-36 health survey. Sensory symptoms were not reported and mild sensory signs were found in six patients. Electrophysiological abnormalities consistent with a diagnosis of neuropathy were found in 16 patients (17%). Peripheral nerve involvement was significantly associated with decreased muscle strength (p = 0.001) and absence of Achilles-tendon reflexes (p = 0.003), but not with age or duration of neuromuscular symptoms. It had no significant effect on balance, mental or physical health. In conclusion, peripheral nerve involvement may be one of the multisystemic manifestations of DM1, but is usually subclinical. Other causes should be excluded when sensory symptoms or signs are severe.     

The additional yield of combined nerve/muscle biopsy in vasculitic neuropathy

Background: Vasculitic neuropathy can be confirmed by demonstrating vasculitis in a nerve biopsy, but it is uncertain to what extent combined (i.e. nerve/muscle) biopsy improves the yield. Methods: A random‐effects meta‐analysis was performed to assess the additional yield of combined biopsy in vasculitic neuropathy. Medline, Embase, LILACS and ISI were searched from January 1980 until January 2009 for relevant articles on the yield of nerve, muscle or combined biopsy to diagnose vasculitic neuropathy. Fourteen (15%) studies were included. Methodological quality was scored using a modified Quality Assessment for Diagnostic Accuracy Studies tool. Results: In patients clinically suspected of vasculitic neuropathy, the additional yield of definite vasculitis in combined biopsy was 5.1% (95% CI 1.1–9.2%; P = 0.013). In patients diagnosed with vasculitic neuropathy, the additional yield of definite vasculitis in combined biopsy was 15% (95% CI 2.1–28%; P = 0.023). Conclusions: There is a modest additional yield of definite vasculitis in combined biopsy compared to nerve biopsy alone. Because of methodological flaws in analysed studies, the findings should be validated in a prospective study.     

Vasculitic neuropathy: Comparison of clinical predictors with histopathological outcome

Introduction:To improve diagnostic accuracy, in this study we compared prebiopsy clinical parameters with subsequent pathological confirmation of peripheral nerve vasculitis. Methods: Clinical, laboratory, and neurophysiological parameters were analyzed for consecutive patients referred for nerve biopsy with suspected vasculitis. Patients were assigned pathological categories of definite, probable, possible, or absent vasculitis using validated guidelines. Patients with definite or probable vasculitis were considered to have pathologically confirmed vasculitis. Results: From a cohort of 78 patients, biopsy confirmed vasculitis in 29.5%. Parameters that best differentiated between pathologically confirmed and pathologically unlikely vasculitis were stepwise clinical progression (34.8% vs. 5.6%), the presence of serum anti-myeloperoxidase antibody (28.6% vs. 2.2%) and rheumatoid factor seropositivity (38.1% vs. 10.7%). Pathologically absent vasculitis was frequent in patients with normal (100%) or primarily demyelinating (87.5%) nerve conduction studies. Discussion: Factoring the negative predictors of pathologically confirmed vasculitis into decision-making can reduce the frequency of diagnostically unhelpful nerve biopsies. Muscle Nerve 59:643–649, 2019     

Diabetic peripheral neuropathy: A clinicopathologic and immunohistochemical analysis of sural nerve biopsies

We performed quantitative immunohistochemical studies of sural nerve biopsy specimens from 20 patients to determine whether endoneurial and epineurial lymphocytic infiltration occurs in diabetic nerves. The diabetic nerves contained a mean of 129 CD3⁺ cells per tissue section compared to 19 cells in patients with chronic neuropathy matched for the histologic severity of disease, and 0–5 cells in normal control nerves. The T-cell infiltrates in the diabetic nerves were predominantly of the CD8⁺ cell type. Activated endoneurial lymphocytes expressed immunoreactive cytokines and major histocompatibility class II antigens. Microvasculitis was found in 12 (60%) patients. Infiltrative T cells may contribute to the pathogenesis of diabetic neuropathy through a variety of effector mechanisms. © 1996 John Wiley & Sons, Inc.     

Demyelinating Peripheral Neuropathy in Devic Disease

Abstract: This is a report of a 20-year-old man with typical features of Devic disease (neuromyelitis optica) associated with demyelinating peripheral neuropathy. A sural nerve biopsy showed markedly decreased myelinated fibers of a large diameter. Teased fiber preparations showed segmental remyelination in 50% of examined fibers, as well as a few demyelination. Demyelination of bilateral optic nerves, spinal cord, and peripheral nerves at the same time suggests a possibility of common pathogenetic mechanisms in both the central and peripheral nervous systems.     

多发性硬化脊髓型合并周围神经病变

目的：评价多发性硬化（MS）脊髓型的临床特征,脊髓磁共振成像（MRI）,神经电生理检查和腓肠神经活检的诊断价值。方法：分析14例MS脊髓型临床表现,脊髓MRI,神经电生理和腓神经活组织病理检查。结果：其临床表现为两侧肢体不对称性运动和感觉障碍的脊髓内部损害,可伴有发作性症状,有缓解和复发,脊髓MRI可以明确脱髓鞘部位,表现髓内纵行条带状或斑片状长T1长T2信号,脊髓略增粗,诱发电位有极高的敏感性,肌电图和腓肠神经病理提示周围神经脱髓鞘改变。结论：MRI、神经电生理检查及周围神经活检对MS脊髓型的早期诊断和治疗起重要作用。     

Neurofibromatous neuropathy

Three cases of chronic distal sensorimotor neuropathy are described in patients with neurofibromatosis. One had type 2 or central neurofibromatosis with a chromosome 22 deletion; the precise form of the disease was not established in the other two. A striking clinical feature was a diffuse nodular enlargement of the peripheral nerves. Nerve biopsies from all three cases demonstrated the presence of neurofibromatous pathology. Neurofibromatous neuropathy constitutes a rare manifestation of neurofibromatosis, related to diffuse neurofibromatous changes in the peripheral nerves.     

Peripheral neuropathy in young-old and old-old patients.

Diabetes is said to account for most cases of neuropathy in the elderly. We reviewed records of 223 young-old (65-79 years) and 77 old-old (>or=80 years) patients referred for evaluation of neuropathic symptoms over a 9-year period. We prospectively validated our findings in 102 consecutive elderly (77 young-old) patients receiving intensive evaluation for neuropathy. Diabetes was the most common cause of neuropathy (41%), but was less common in the old-old (25% versus 46%, P < 0.001). Idiopathic neuropathies were more common in the old-old (39% versus 9%, P < 0.001). Alcoholic and nutritional neuropathies were uncommon in the old-old. Electrophysiological studies showed that most patients had an axonal type of neuropathy. Sural and peroneal response amplitudes were poorly correlated with age. We obtained similar results in our prospective study. The distribution of causes of neuropathies in young-old and old-old patients, in a hospital-based sample, is age-related. Future studies need to include the old-old to better understand the nature of neuropathy in the elderly.     

EFNS guidelines on the use of skin biopsy in the diagnosis of peripheral neuropathy

Skin biopsy has become a widely used tool to investigate small calibre sensory nerves including somatic unmyelinated intraepidermal nerve fibres (IENF), dermal myelinated nerve fibres, and autonomic nerve fibres in peripheral neuropathies and other conditions. Different techniques for tissue processing and nerve fibre evaluation have been used. In March 2004, a Task Force was set up under the auspices of the European Federation of Neurological Societies (EFNS) with the aim of developing guidelines on the use of skin biopsy in the diagnosis of peripheral neuropathies. We searched the Medline database from 1989, the year of the first publication describing the innervation of human skin using immunostaining with anti-protein-gene-product 9.5 (PGP 9.5) antibodies, to 31 March 2005. All pertinent papers were rated according to the EFNS guidance. The final version of the guidelines was elaborated after consensus amongst members of the Task Force was reached. For diagnostic purposes in peripheral neuropathies, we recommend performing a 3-mm punch skin biopsy at the distal leg and quantifying the linear density of IENF in at least three 50-mum thick sections per biopsy, fixed in 2% PLP or Zamboni's solution, by bright-field immunohistochemistry or immunofluorescence with anti-PGP 9.5 antibodies (level A recommendation). Quantification of IENF density closely correlated with warm and heat-pain threshold, and appeared more sensitive than sensory nerve conduction study and sural nerve biopsy in diagnosing small-fibre sensory neuropathy. Diagnostic efficiency and predictive values of this technique were very high (level A recommendation). Confocal microscopy may be particularly useful to investigate myelinated nerve fibres, dermal receptors and dermal annex innervation. In future, the diagnostic yield of dermal myelinated nerve fibre quantification and of sweat gland innervation should be addressed. Longitudinal studies of IENF density and regeneration rate are warranted to correlate neuropathological changes with progression of neuropathy and to assess the potential usefulness of skin biopsy as an outcome measure in peripheral neuropathy trials (level B recommendation). In conclusion, punch skin biopsy is a safe and reliable technique (level A recommendation). Training in an established cutaneous nerve laboratory is recommended before using skin biopsy as a diagnostic tool in peripheral neuropathies. Quality control at all levels is mandatory.     

Intranervous immunoglobulin deposits: an underestimated mechanism of neuropathy

There are several pathogenic mechanisms of peripheral nerve involvement in patients with monoclonal dysglobulinemia. Intranervous proliferation of malignant cells, immunoglobulin, or amyloid deposits in the endoneurial space can only be determined by examination of nerve biopsy specimens. We present clinical, electrophysiological, and histological data from seven patients whose polyneuropathy was induced by immunoglobulin deposits in the endoneurial space. As these lesions cannot be demonstrated on clinical and electrophysiological grounds, the indication for nerve biopsy derives from careful analysis of each patient presenting with a polyneuropathy and a monoclonal dysglobulinemia. To visualize and clearly characterize these deposits, electron microscopic examination is indispensable. Immunocytochemical methods using both light and electron microscopy for ultrastructural analysis are of great value. Demonstration of endoneurial immunoglobulin deposits may have major therapeutic consequences. Indeed, identification of these deposits prompted the use of aggressive treatment, which was quite effective in five of our seven patients.     

Progressive idiopathic axonal neuropathy

Abstract. Patients with a progressive disabling idiopathic axonal neuropathy could have a potentially treatable immune mediated neuropathy. To evaluate whether progressive idiopathic axonal neuropathy could be a pathologically difficult to prove vasculitic neuropathy pathologically difficult to prove or if it could be a separate clinical entity (i. e. with the axon as the primary immunological target), we performed a comparative clinical and histopathological study in 10 patients with progressive idiopathic axonal neuropathy, 10 patients with vasculitic neuropathy, and 12 patients with chronic idiopathic axonal polyneuropathy (CIAP). The clinical features and disease course in patients with progressive idiopathic axonal neuropathy and patients with vasculitic neuropathy were similar. Six patients with progressive idiopathic axonal neuropathy had been treated with prednisone and/or intravenous immunoglobulin. Disability decreased in all these six patients, but also in two of the four non-treated patients. Upon reviewing the sural nerve biopsy specimens, vasculitis was found in one patient with progressive idiopathic axonal neuropathy. Vasculitis-associated signs of ischemic injury or inflammation (most notably: large variation in fascicular axonal degeneration, perivascular inflammation, inflammation of the blood vessel wall without lumen obstruction) were found in four patients with progressive idiopathic axonal neuropathy, in all patients with vasculitic neuropathy, but were absent in patients with CIAP. The findings show that there is a small chance of finding sural nerve vasculitis upon scrutinising biopsy examination in progressive idiopathic axonal neuropathy. The presence of vasculitisassociated signs in progressive idiopathic axonal neuropathy suggests that some of these patients could have vasculitic neuropathy, even if vasculitic lesions cannot be demonstrated. However, if inflammatory changes cannot be demonstrated this does not preclude an immune-mediated origin.     

The yield of sural nerve biopsy in the evaluation of peripheral neuropathies

The diagnostic yield of sural nerve biopsy was evaluated in 120 peripheral neuropathy patients. In 58 (48%) a final diagnosis was reached without biopsy, while 14 (11.5%) remained undiagnosed. Nerve biopsy contributed to the final diagnosis in 20 of the 53 biopsies (38%). In patients with motor conduction velocity below 30 m/s, sural nerve histology was helpful in 65% of biopsies. In patients with milder reduction in conduction biopsy contributed in only 11%. It is concluded that in general neurological population, nerve biopsy is of limited value as a routine diagnostic procedure. However, in patients with marked slowing of conduction velocity, in whom the diagnosis is not immediately apparent, sural nerve biopsy is indicated.     

Skin biopsy-proven flecainide-induced neuropathy

Flecainide acetate is a classic Ic antiarrhythmic agent used to treat a variety of cardiac arrhythmias. Non-cardiac side effects usually affect the central nervous system. Few case reports of possible flecainide-induced peripheral neuropathy have been reported. We report this unique case in that flecainide-induced sensory neuropathy was confirmed with skin biopsy, and subsequent improvement of neuropathy was documented with assessment of intraepidermal nerve fiber density in a repeat nerve biopsy.     

Peripheral neuropathy in systemic lupus erythematosus – a longitudinal study

OBJECTIVE: Peripheral neuropathy (PN) is reported to occur in 5-27% of patients with systemic lupus erythematosus (SLE) mostly as a length-dependent sensorimotor axonopathy. Studies over time have not been performed. Design - Longitudinal study. Subjects and Methods: Thirty-three Caucasian SLE patients consented to participate in the study and were subjected to clinical examination, laboratory tests, and nerve conduction velocity (NCV) studies. At the follow-up 7 years later, 7 patients (21%) were dead, 4 refused to participate, and 2 did not want to perform NCV studies. Twenty patients were thus available for longitudinal study. RESULTS: When all SLE patients were considered on a group basis at follow-up, 8 (33%) out of 24 NCV parameters showed significant deterioration despite correction for time, while 16 (67%) were unchanged. Analysis of change from baseline showed that, except for F-responses, several NCV changes were highly dependent (negative regression coefficients) on baseline levels at start of study. No demographic, laboratory, or disease associated quantitative factor was associated with these changes in NCV parameters over time. Nor was a consistent effect on NCV parameters from any qualitative demographic or disease associated factor confirmed by Repeated Measures ANOVA analyses. CONCLUSIONS: A modest progressive neuropathic process exists in patients with SLE. Important is also the finding that, over time, the abnormalities of NCV parameters fluctuate in the individual patients, and the impairments are not necessarily irreversible. This study also shows no association to medication, demographic-, or other disease associated factors.     

糖尿病性周围神经病患者受累神经的分布特点

目的 探讨糖尿病件周围神经病(DPN)患者受累神经的分布特点.方法 对900例2型糖尿病并发DPN患者进行感觉及运动神经传导速度检测,对受累神经的分布进行分析.结果 本组感觉神经异常率为89.3%;包括65.2%(587例)的正中神经、38.9%(350例)的尺神经、89.3%(804例)的腓浅神经、60.4%(544例)的腓肠神经及29.6%(64例)的胫后神经异常.运动神经异常率为34.5%;包括32.1%(289例)的正中神经、28.7%(258例)的腓总神经、22.7%(49例)的胫神经异常.感觉神经异常率明显高于运动神经异常率(P<0.01);下肢感觉神经异常率明显高于上肢(P<0.01).结论 DPN患者受累的感觉神经以腓浅神经、正中神经、腓肠神经最普遍,受累的运动神经以正中神经、腓总神经为多见.