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Doneddu PE, Borroni R, Ceribelli A, Carta F, Sechi M, Moretti GS, Giordano A, Scheveger F, Moret F, Fernandes M, Gentile F, Valenti M, Luciano N, Bianchi E, Costanzo A, De Nittis PE, Selmi C, Nobile-Orazio E. Risk of peripheral neuropathy in patients with psoriasis and psoriatic arthritis. A prospective cohort study. Muscle Nerve 2024; 70:371-378. [PMID: 38940240 DOI: 10.1002/mus.28196] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2023] [Revised: 06/12/2024] [Accepted: 06/15/2024] [Indexed: 06/29/2024]
Abstract
INTRODUCTION/AIMS Laboratory and clinical data suggest a link between neurologically mediated inflammation and psoriasis, but the risk and features of peripheral neuropathy in psoriasis or psoriatic arthritis remain unknown. The aim of this exploratory study was to evaluate the risk and to describe the features of peripheral neuropathy in patients with psoriasis and psoriatic arthritis. METHODS One hundred patients with psoriasis and/or psoriatic arthritis and 100 control subjects were consecutively enrolled. Diagnostic confirmation included electrophysiological examination, skin biopsy, and nerve ultrasound for confirmed polyneuropathy. RESULTS Nine patients were diagnosed with confirmed polyneuropathy, while none of the control subjects had the condition (relative risk [RR] = 19.00, 95% confidence interval [CI] = 1.12-322.11). Specific relative risks for polyneuropathy were 22.09 (95% CI = 1.17-416.43) in psoriasis patients and 18.75 (95% CI = 1.07-327.62) in psoriatic arthritis patients. The observed polyneuropathy in all nine patients was length-dependent, symmetrical, and predominantly sensory, with minimal or no disability. Comorbidities and exposure to therapies known to increase the risk of polyneuropathy were more frequent in psoriasis and/or psoriatic arthritis patients compared to controls (42% vs. 4%, p = .0001). Analyzing data after excluding possible contributory causes, the risk of polyneuropathy in patients with psoriasis and/or psoriatic arthritis was not significant. DISCUSSION Psoriasis and psoriatic arthritis appear to be associated with an increased risk of polyneuropathy. This increased risk seems to be linked to the higher prevalence of contributing factors for polyneuropathy, rather than a direct increase in neuropathy risk specifically related to psoriasis and psoriatic arthritis.
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Affiliation(s)
- Pietro E Doneddu
- Neuromuscular and Neuroimmunology Unit, IRCCS Humanitas Research Hospital, Milan, Italy
- Department of Biomedical Sciences, Humanitas University, Milan, Italy
| | - Riccardo Borroni
- Department of Biomedical Sciences, Humanitas University, Milan, Italy
- Dermatology Unit, Humanitas Research Hospital, IRCCS, Milan, Italy
| | - Angela Ceribelli
- Division of Rheumatology and Clinical Immunology, IRCCS Humanitas Research Hospital, Milan, Italy
| | - Francesca Carta
- Neuromuscular and Neuroimmunology Unit, IRCCS Humanitas Research Hospital, Milan, Italy
| | - Margherita Sechi
- Neuromuscular and Neuroimmunology Unit, IRCCS Humanitas Research Hospital, Milan, Italy
| | - Giulia S Moretti
- Neuromuscular and Neuroimmunology Unit, IRCCS Humanitas Research Hospital, Milan, Italy
| | - Andrea Giordano
- Neuromuscular and Neuroimmunology Unit, IRCCS Humanitas Research Hospital, Milan, Italy
| | - Francesco Scheveger
- Neuromuscular and Neuroimmunology Unit, IRCCS Humanitas Research Hospital, Milan, Italy
| | - Federica Moret
- Neuromuscular and Neuroimmunology Unit, IRCCS Humanitas Research Hospital, Milan, Italy
| | - Marco Fernandes
- Neuromuscular and Neuroimmunology Unit, IRCCS Humanitas Research Hospital, Milan, Italy
| | - Francesco Gentile
- Neuromuscular and Neuroimmunology Unit, IRCCS Humanitas Research Hospital, Milan, Italy
| | - Mario Valenti
- Department of Biomedical Sciences, Humanitas University, Milan, Italy
- Dermatology Unit, Humanitas Research Hospital, IRCCS, Milan, Italy
| | - Nicoletta Luciano
- Division of Rheumatology and Clinical Immunology, IRCCS Humanitas Research Hospital, Milan, Italy
| | - Elisa Bianchi
- Laboratorio di Malattie Neurologiche, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Italy
| | - Antonio Costanzo
- Department of Biomedical Sciences, Humanitas University, Milan, Italy
- Dermatology Unit, Humanitas Research Hospital, IRCCS, Milan, Italy
| | | | - Carlo Selmi
- Department of Biomedical Sciences, Humanitas University, Milan, Italy
- Division of Rheumatology and Clinical Immunology, IRCCS Humanitas Research Hospital, Milan, Italy
| | - Eduardo Nobile-Orazio
- Neuromuscular and Neuroimmunology Unit, IRCCS Humanitas Research Hospital, Milan, Italy
- Department of Medical Biotechnology and Translational Medicine, Milan University, Milan, Italy
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Androutsakos T, Tsantzali I, Karagiannakis DS, Flevari P, Iakovou D, Pouliakis A, Kykalos S, Doris S, Xyla V. Peripheral Neuropathy in Patients with Hepatitis C Infection-Reversibility after HCV Eradication: A Single Center Study. Viruses 2024; 16:522. [PMID: 38675865 PMCID: PMC11054011 DOI: 10.3390/v16040522] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2024] [Revised: 03/22/2024] [Accepted: 03/24/2024] [Indexed: 04/28/2024] Open
Abstract
Chronic hepatitis C virus (HCV) infection is characterized by a variety of extra-hepatic manifestations; peripheral neuropathy (PN) is one of the most common, especially when mixed cryoglobulinemia (MCG) is present. The prevalence and risk factors of HCV-related PN in the absence of MCG are largely unknown. We conducted a prospective, single-center study, examining the prevalence and reversibility of HCV-associated neuropathy in the absence of MCG. Nerve fiber density in the epidermis was evaluated through skin biopsy and electroneurography (ENG) before HCV-treatment initiation and 1 year post sustained virological remission (SVR). Forty HCV-infected individuals (nine HIV co-infected) with no other neuron-harming factors were included; four other HCV mono- and three HIV co-infected individuals were excluded due to presence of diabetes, B12 insufficiency, or neurotoxic drugs. Twelve consecutive controls with no neuron-harming conditions were also recruited; eight more were excluded due to meeting exclusion criteria. Four patients had ENG signs of polyneuropathy (two with HCV mono- and two with HIV co-infection), while seven more (five with HCV mono- and two with HIV co-infection) had signs of mono-neuropathy, leading to PN prevalences of 22.5% and 44% for mono- and co-infection, respectively (p value 0.179). The two patients with HCV mono-infection and polyneuropathy and the one with ulnar nerve damage showed ENG improvement 1 year post SVR. Regarding intraepidermal nerve density, HCV infection, irrespective of HIV co-infection, was correlated with a lower intraepidermal neuron density that improved 1 year post SVR (p value 0.0002 for HCV and 0.0326 for HCV/HIV co-infected patients). PN is common in HCV infection; successful eradication of HCV leads to PN improvement.
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Affiliation(s)
- Theodoros Androutsakos
- Department of Pathophysiology, National and Kapodistrian University of Athens, 115 27 Athens, Greece;
| | - Ioanna Tsantzali
- Second Department of Neurology, School of Medicine, National and Kapodistrian University of Athens, “Attikon” General University Hospital, 124 62 Athens, Greece;
| | - Dimitrios S. Karagiannakis
- Academic Department of Gastroenterology, Laiko General Hospital, National and Kapodistrian University of Athens, 115 27 Athens, Greece;
| | - Pagona Flevari
- Centre of Excellence in Rare Haematological (Haemoglobinopathies) & Rare Metabolic (Gaucher Disease) Diseases, Laiko General Hospital, 115 27 Athens, Greece;
| | - Despoina Iakovou
- West Suffolk Hospital NHS Foundation Trust, Bury St Edmunds IP33 2QZ, UK;
| | - Abraham Pouliakis
- Second Department of Pathology, National and Kapodistrian University of Athens, 124 62 Athens, Greece;
| | - Stylianos Kykalos
- Second Department of Propaedeutic Surgery, National and Kapodistrian University of Athens, 115 27 Athens, Greece;
| | - Stylianos Doris
- Neurology Department, Metropolitan General Hospital, 155 62 Athens, Greece;
| | - Vasileia Xyla
- Department of Pathophysiology, National and Kapodistrian University of Athens, 115 27 Athens, Greece;
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Boegle AK, Narayanaswami P. Infectious Neuropathies. Continuum (Minneap Minn) 2023; 29:1418-1443. [PMID: 37851037 DOI: 10.1212/con.0000000000001334] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2023]
Abstract
OBJECTIVE This article discusses the clinical manifestations and management of infectious peripheral neuropathies. LATEST DEVELOPMENTS Several infectious etiologies of peripheral neuropathy are well-recognized and their treatments are firmly established. The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is associated with several central and peripheral nervous system manifestations, including peripheral neuropathies. Additionally, some COVID-19 vaccines have been associated with Guillain-Barré syndrome. These disorders are an active area of surveillance and research. Recent evidence-based guidelines have provided updated recommendations for the diagnosis and treatment of Lyme disease. ESSENTIAL POINTS Infectious agents of many types (primarily bacteria and viruses) can affect the peripheral nerves, resulting in various clinical syndromes such as mononeuropathy or mononeuropathy multiplex, distal symmetric polyneuropathy, radiculopathy, inflammatory demyelinating polyradiculoneuropathy, and motor neuronopathy. Knowledge of these infections and the spectrum of peripheral nervous system disorders associated with them is essential because many have curative treatments. Furthermore, understanding the neuropathic presentations of these disorders may assist in diagnosing the underlying infection.
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De León AM, Garcia-Santibanez R, Harrison TB. Article Topic: Neuropathies Due to Infections and Antimicrobial Treatments. Curr Treat Options Neurol 2023; 25:1-17. [PMID: 37360749 PMCID: PMC10256960 DOI: 10.1007/s11940-023-00756-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/10/2023] [Indexed: 06/28/2023]
Abstract
Purpose of eview The aim of this review is to discuss the presentation, diagnosis, and management of polyneuropathy (PN) in selected infections. Overall, most infection related PNs are an indirect consequence of immune activation rather than a direct result of peripheral nerve infection, Schwann cell infection, or toxin production, though note this review will describe infections that cause PN through all these mechanisms. Rather than dividing them by each infectious agent separately, we have grouped the infectious neuropathies according to their presenting phenotype, to serve as a guide to clinicians. Finally, toxic neuropathies related to antimicrobials are briefly summarized. Recent findings While PN from many infections is decreasing, increasing evidence links infections to variants of GBS. Incidence of neuropathies secondary to use of HIV therapy has decreased over the last few years. Summary In this manuscript, a general overview of the more common infectious causes of PN will be discussed, dividing them across clinical phenotypes: large- and small-fiber polyneuropathy, Guillain-Barré syndrome (GBS), mononeuritis multiplex, and autonomic neuropathy. Rare but important infectious causes are also discussed.
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Affiliation(s)
- Andrés M. De León
- Neuromuscular Division Department of Neurology, Emory University, Executive Park 12 NE, GA 30329 Atlanta, USA
| | - Rocio Garcia-Santibanez
- Neuromuscular Division Department of Neurology, Emory University, Executive Park 12 NE, GA 30329 Atlanta, USA
| | - Taylor B. Harrison
- Division of Neuromuscular Medicine, Department of Neurology, Emory University School of Medicine, 83 Jessie Junior Drive Box 039, Atlanta, GA 30303 USA
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Relapse of Hepatitis C Virus Cryoglobulinemic Vasculitis After Sustained Viral Response After Interferon-Free Direct-Acting Antivirals. Am J Gastroenterol 2022; 117:627-636. [PMID: 35103020 DOI: 10.14309/ajg.0000000000001667] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/07/2021] [Accepted: 01/20/2022] [Indexed: 12/11/2022]
Abstract
INTRODUCTION Direct-acting antiviral agents (DAAs) have modified the management of chronic hepatitis C virus (HCV) infection, including HCV-related cryoglobulinemic vasculitis (CryoVas). However, patients might experience vasculitis relapse, and no reliable predictors of CryoVas relapse after sustained virologic response (SVR) have been established. We aimed to describe HCV-CryoVas relapse rates and factors associated with it. METHODS An international multicenter cohort where patients with HCV-CryoVas from Egypt, France, and Italy treated with DAA were analyzed retrospectively. Factors associated with relapse-free survival were evaluated in a multivariate-adjusted model. RESULTS Of 913 patients, 911 (99.8%) obtained SVR. After 35 months of the median follow-up, 798 patients (87.4%) had sustained remission of vasculitis, while 115 (12.6%) experienced CryoVas relapse. By the time of relapse, skin involvement was present in 100%, renal involvement in 85.2%, and peripheral neuropathy in 81.7%. Relapses were treated with glucocorticoids in 90.9%, associated with plasma exchange, cyclophosphamide, or rituximab in 50%, 37.3%, and 6.4%, respectively. The cumulative incidence of CryoVas relapse was 0.7% (95% CI 0.3-1.4), 12.3% (95% CI 10.2-14.6), and 13.1% (95% CI 11.0-15.5) at 12, 24, and 36 months after DAA treatment, respectively. Independent baseline risk factors associated with CryoVas relapse were male sex, skin ulcers, kidney involvement at baseline, and peripheral neuropathy at the end of DAA treatment. Death occurred in 11 relapsers, mainly due to infections. DISCUSSION A substantial proportion of patients with CryoVas experience relapse after DAA-induced SVR. Relapses are moderate-to-severe and affect survival after 24 months, mainly due to infections. Independent risk factors for relapse or death were found.
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Marascio N, Rotundo S, Quirino A, Matera G, Liberto MC, Costa C, Russo A, Trecarichi EM, Torti C. Similarities, differences, and possible interactions between hepatitis E and hepatitis C viruses: Relevance for research and clinical practice. World J Gastroenterol 2022; 28:1226-1238. [PMID: 35431515 PMCID: PMC8968488 DOI: 10.3748/wjg.v28.i12.1226] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/05/2021] [Revised: 01/06/2022] [Accepted: 02/23/2022] [Indexed: 02/06/2023] Open
Abstract
Hepatitis E virus (HEV) and hepatitis C virus (HCV) are both RNA viruses with a tropism for liver parenchyma but are also capable of extrahepatic manifestations. Hepatitis E is usually a viral acute fecal-oral transmitted and self-limiting disease presenting with malaise, jaundice, nausea and vomiting. Rarely, HEV causes a chronic infection in immunocompromised persons and severe fulminant hepatitis in pregnant women. Parenteral HCV infection is typically asymptomatic for decades until chronic complications, such as cirrhosis and cancer, occur. Despite being two very different viruses in terms of phylogenetic and clinical presentations, HEV and HCV show many similarities regarding possible transmission through organ transplantation and blood transfusion, pathogenesis (production of antinuclear antibodies and cryoglobulins) and response to treatment with some direct-acting antiviral drugs. Although both HEV and HCV are well studied individually, there is a lack of knowledge about coinfection and its consequences. The aim of this review is to analyze current literature by evaluating original articles and case reports and to hypothesize some interactions that can be useful for research and clinical practice.
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Affiliation(s)
- Nadia Marascio
- Department of Health Sciences, Unit of Microbiology, University “Magna Graecia” of Catanzaro, Catanzaro 88100, Italy
| | - Salvatore Rotundo
- Department of Medical and Surgical Sciences, Unit of Infectious and Tropical Diseases, "Magna Graecia" University of Catanzaro, Catanzaro 88100, Italy
| | - Angela Quirino
- Department of Health Sciences, Unit of Microbiology, University “Magna Graecia” of Catanzaro, Catanzaro 88100, Italy
| | - Giovanni Matera
- Department of Health Sciences, Unit of Microbiology, University “Magna Graecia” of Catanzaro, Catanzaro 88100, Italy
| | - Maria Carla Liberto
- Department of Health Sciences, Unit of Microbiology, University “Magna Graecia” of Catanzaro, Catanzaro 88100, Italy
| | - Chiara Costa
- Department of Medical and Surgical Sciences, Unit of Infectious and Tropical Diseases, "Magna Graecia" University of Catanzaro, Catanzaro 88100, Italy
| | - Alessandro Russo
- Department of Medical and Surgical Sciences, Unit of Infectious and Tropical Diseases, "Magna Graecia" University of Catanzaro, Catanzaro 88100, Italy
| | - Enrico Maria Trecarichi
- Department of Medical and Surgical Sciences, Unit of Infectious and Tropical Diseases, "Magna Graecia" University of Catanzaro, Catanzaro 88100, Italy
| | - Carlo Torti
- Department of Medical and Surgical Sciences, Unit of Infectious and Tropical Diseases, "Magna Graecia" University of Catanzaro, Catanzaro 88100, Italy
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Huang CC, Wu KL, Liu JS, Chang YY. Autonomic impairment in treatment-naive patients with chronic hepatitis B and C infections. Auton Neurosci 2022; 238:102928. [PMID: 35021146 DOI: 10.1016/j.autneu.2021.102928] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2021] [Revised: 11/16/2021] [Accepted: 12/10/2021] [Indexed: 10/19/2022]
Abstract
BACKGROUND Peripheral neuropathy is not an uncommon manifestation in patients with chronic hepatitis. The role of cryoglobulin (CG) in neuropathy in patients with chronic hepatitis remains controversial. There is limited information about the autonomic neuropathy in chronic hepatitis. This study aimed to evaluate autonomic function in treatment-naive patients with chronic hepatitis B or hepatitis C infection and to elucidate the association between autonomic neuropathy and CG in these patients. METHODS A total of 29 treatment-naive patients with chronic, yet mild degrees of hepatitis B or C infection were evaluated for autonomic function, including those in the sympathetic sudomotor, cardiovagal, and adrenergic domains, to compare with the control subjects. The autonomic impairment was graded using the Composite Autonomic Scoring Scale. Then, association analyses between autonomic parameters/scores and CG were performed. RESULTS Patients with chronic hepatitis B or C infection had significantly worse autonomic function than control subjects, especially in the sudomotor and cardiovagal domains. The autonomic manifestations in cases with and without CG were similar. There was no significant difference in autonomic dysfunction between patients with hepatitis B and C infections. CONCLUSION The study demonstrated that autonomic neuropathy was not uncommon in patients with chronic hepatitis B or C infection. There was no association between autonomic neuropathy and CG.
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Affiliation(s)
- Chih-Cheng Huang
- Department of Neurology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University, College of Medicine, Kaohsiung, Taiwan
| | - Keng-Liang Wu
- Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University, College of Medicine, Kaohsiung, Taiwan
| | - Jia-Shou Liu
- Department of Neurology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University, College of Medicine, Kaohsiung, Taiwan
| | - Yung-Yee Chang
- Department of Neurology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University, College of Medicine, Kaohsiung, Taiwan.
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Elkholy MM, Eid RA. Quantitative motor unit potential analysis and nerve conduction studies for detection of subclinical peripheral nerve dysfunction in patients with compensated liver cirrhosis. THE EGYPTIAN JOURNAL OF NEUROLOGY, PSYCHIATRY AND NEUROSURGERY 2021. [DOI: 10.1186/s41983-021-00348-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
Abstract
Abstract
Background
Peripheral neuropathy is an underestimated problem of compensated liver cirrhosis despite its negative effect on quality of life. The aim was to assess the role of meticulous electrophysiological screening (nerve conduction responses and quantitative motor unit potential analysis) of subclinical peripheral nerve dysfunction in patients with compensated cirrhosis and also to explore its relations with different characteristics of liver disease. Severity of cirrhosis was assessed by Child–Pugh and albumin-bilirubin (ALBI) scores.
Results
Prevalence of hepatic neuropathy (HN) was 82%. It involved sensory and motor fibers (66%), and its pathophysiology was axonal (53.7%) or mixed axonal and demyelinating (46.3). The most sensitive discriminating tests were ulnar sensory conduction velocity (area under curve (AUC) = 0.915) and peak latency (AUC = 0.887), peroneal motor conduction velocity (AUC = 0.885), ulnar distal motor latency (AUC = 0.842), and first dorsal interosseous number of phases (AUC = 0.736). HN showed significant correlation with the severity of liver disease assessed by both child (P = 0.029) and ALBI (P = 0.016) scores and also correlated with the low serum albumin level (P = 0.001).
Conclusions
Subclinical mild axonal polyneuropathy is very common in post-hepatitis C compensated cirrhosis picked up by meticulous electrophysiological testing, and it is related to severity of liver cirrhosis and low serum albumin level.
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Zanone MM, Marinucci C, Ciancio A, Cocito D, Zardo F, Spagone E, Ferrero B, Cerruti C, Charrier L, Cavallo F, Saracco GM, Porta M. Peripheral neuropathy after viral eradication with direct-acting antivirals in chronic HCV hepatitis: A prospective study. Liver Int 2021; 41:2611-2621. [PMID: 34219359 PMCID: PMC8596576 DOI: 10.1111/liv.15002] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/25/2021] [Revised: 06/16/2021] [Accepted: 06/21/2021] [Indexed: 01/13/2023]
Abstract
BACKGROUND HCV-related extra-hepatic complications include peripheral neuropathies, with important prevalence and impact. A recent metanalysis of previous intervention trials concluded for insufficient data to support evidence-based treatments for this complication. In this longitudinal study, we assessed for the first time prevalence and outcome of neuropathy in a cohort of patients with chronic HCV, before and after direct-acting antiviral agent (DAA) treatment. METHOD Ninety-four patients (mean age 58.5 ± 9.9, infection duration 22.2 ± 6.3 years) without systemic and metabolic diseases, underwent neurological examination and electroneurography studies before (T0) and 10.4 ± 1.7 months after the end of DAA therapy (T1), and cryoglobulins (CG) assessment. Muscle strength was evaluated by Medical Research Council (MRC) score; neuropathic pain, sensory function, disability, quality of life were assessed by validated questionnaires (DN4, NPSI, SSS, INCAT and Euro-QoL). RESULTS At T0, sensory-motor neuropathy was detected in 22 patients (23%), reflexes were depressed in 32 (34%) with no association with infection duration, viral load, age, CG. Neuropathic pain (DN4 ≥4) was present in 37 patients (39%). At T1, out of the 22 patients with altered electroneurography, 3 had died or developed HCC, 4 showed normal electroneurography, and nerve amplitude parameters tended to improve in the whole group. Only 11 patients (12%) had depressed reflexes and 10 (11%) DN4 ≥4 (P < .05 compared to T0). Scores for MRC, questionnaires and Euro-QoL improved significantly (P < .05). CONCLUSION Our study confirms the high prevalence of clinical and subclinical peripheral sensory-motor neuropathy in patients with HCV infection and indicates improvement after eradication by DAA. These results support the need for larger intervention studies.
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Affiliation(s)
- Maria M. Zanone
- Internal Medicine 1Department of Medical SciencesUniversity of TurinTorinoItaly
| | - Claudia Marinucci
- Internal Medicine 1Department of Medical SciencesUniversity of TurinTorinoItaly
| | - Alessia Ciancio
- Division of Gastroenterology and HepathologyDepartment of Medical SciencesUniversity of TurinTorinoItaly
| | - Dario Cocito
- Department of NeurosciencesUniversity of TurinTorinoItaly
| | - Federica Zardo
- Internal Medicine 1Department of Medical SciencesUniversity of TurinTorinoItaly
| | | | - Bruno Ferrero
- Department of NeurosciencesUniversity of TurinTorinoItaly
| | - Cristina Cerruti
- Internal Medicine 1Department of Medical SciencesUniversity of TurinTorinoItaly
| | - Lorena Charrier
- Department of Public Health and PaediatricsUniversity of TurinTorinoItaly
| | - Franco Cavallo
- Department of Public Health and PaediatricsUniversity of TurinTorinoItaly
| | - Giorgio M. Saracco
- Division of Gastroenterology and HepathologyDepartment of Medical SciencesUniversity of TurinTorinoItaly
| | - Massimo Porta
- Internal Medicine 1Department of Medical SciencesUniversity of TurinTorinoItaly
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Abstract
PURPOSE OF REVIEW This article describes the neurologic sequelae of various nutritional micronutrient deficiencies, celiac disease, inflammatory bowel disease, and liver disease. Where relevant, appropriate treatments for these conditions are also discussed. The developing field of the microbiome and nervous system interaction is also outlined. RECENT FINDINGS Pathology in the gastrointestinal system can affect the nervous system when it causes micronutrient deficiency, when immune responses created by the gastrointestinal system affect the nervous system, when toxins caused by gastrointestinal organ failure harm the nervous system, and when treatments aimed at a gastrointestinal medical condition cause damage to the nervous system as a side effect. SUMMARY This article addresses familiar concepts and new developments in the treatment and understanding of diseases that affect the gut and nervous system simultaneously.
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Kaur D, Tiwana H, Stino A, Sandroni P. Autonomic neuropathies. Muscle Nerve 2020; 63:10-21. [PMID: 32926436 DOI: 10.1002/mus.27048] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2020] [Revised: 08/07/2020] [Accepted: 08/11/2020] [Indexed: 12/17/2022]
Abstract
Autonomic 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.
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Affiliation(s)
- Divpreet Kaur
- Department of Neurology, Penn State College of Medicine, Hershey, Pennsylvania, USA
| | - Harmanpreet Tiwana
- Department of Neurology, Dartmouth-Hitchcok Medical Center, Lebanon, New Hampshire, USA
| | - Amro Stino
- Department of Neurology, Division of Neuromuscular Medicine, University of Michigan School of Medicine, Ann Arbor, Michigan, USA
| | - Paola Sandroni
- Department of Neurology, Mayo Clinic, Rochester, Minnesota, USA
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Severe Guillain-Barré syndrome associated with chronic active hepatitis C and mixed cryoglobulinemia: a case report. BMC Infect Dis 2019; 19:636. [PMID: 31315560 PMCID: PMC6637463 DOI: 10.1186/s12879-019-4278-7] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2018] [Accepted: 07/11/2019] [Indexed: 12/14/2022] Open
Abstract
Background We describe a case of severe Guillain-Barre syndrome (GBS) associated with chronic active hepatitis C and mixed cryoglobulinemia (MC). To our knowledge, this association between GBS and hepatitis C virus (HCV) infection has been rarely reported. Case presentation A 56-year-old man developed symmetrical muscle weakness in all extremities, areflexia and sensorial disorder followed by acute respiratory failure associated with chronic active hepatitis C, which was confirmed by the presence of anti-HCV antibodies in the serum and persistence of HCV RNA viral load for more than 6 months. Chronic hepatitis C was further complicated by type 3 MC. Electromyography showed peripheral nerve injury (mainly in axon). A severe acute motor sensory axonal neuropathy (AMSAN) was diagnosed. After treatment with intravenous immunoglobulin and plasma exchange followed by antiviral therapy by direct-acting antiviral agent, patient showed progressive recovery and was transferred 3 months after his first admission to a rehabilitation center. Conclusions Our case reported a severe GBS associated with HCV infection and MC. EMG classified for the first time the subtype of GBS (severe AMSAN) correlated with severe clinical form. HCV infection should be screened in high-risk patients to prevent silent progression of the chronic hepatitis C and its potentially severe extra-hepatic manifestations.
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McCorquodale D, Smith AG. Clinical electrophysiology of axonal polyneuropathies. HANDBOOK OF CLINICAL NEUROLOGY 2019; 161:217-240. [PMID: 31307603 DOI: 10.1016/b978-0-444-64142-7.00051-5] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
Axonal neuropathies encompass a wide range of acquired and inherited disorders with electrophysiologic characteristics that arise from the unique neurophysiology of the axon. Accurate interpretation of nerve conduction studies and electromyography requires an in-depth understanding of the pathophysiology of the axon. Here we review the unique neurophysiologic properties of the axon and how they relate to clinical electrodiagnostic features. We review the length-dependent Wallerian or "dying-back" processes as well as the emerging body of literature from acquired axonal neuropathies that highlights the importance of axonal disease at the nodes of Ranvier. Neurophysiologic features of individual inherited and acquired axonal diseases, including primary nerve disease as well as systemic immune mediated, metabolic, and toxic diseases involving the peripheral nerve, are reviewed. This comprehensive review of electrodiagnostic findings coupled with the current understanding of pathophysiology will aid the clinician in the evaluation of axonal polyneuropathies.
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Affiliation(s)
- Donald McCorquodale
- Department of Neurology, Virginia Commonwealth University, Richmond, VA, United States
| | - A Gordon Smith
- Department of Neurology, Virginia Commonwealth University, Richmond, VA, United States.
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Wojtowicz M, Wilkowski P, Hryniewiecka E, Cieciura T, Paczek L, Ciszek M. Effect of Successful Treatment of Hepatitis C Virus Infection Recurrence With Direct-Acting Antiviral Agents on Physical Performance in Liver Transplant Recipients. Transplant Proc 2018; 50:2027-2030. [PMID: 30177103 DOI: 10.1016/j.transproceed.2018.02.109] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/25/2017] [Accepted: 02/06/2018] [Indexed: 11/19/2022]
Abstract
BACKGROUND Hepatitis C virus (HCV) infection deregulates function of many organs and systems, affecting patient's daily functioning. The results of treatment of HCV infection recurrence after liver transplantation have improved significantly as a result of the introduction of direct-acting antiviral agents (DAA). This study was aimed at prospective assessment of the effect of HCV elimination with DAA on physical performance of liver transplant recipients. METHODS Eight women and 21 men, median age 61.3 (range, 20.1-71.5) years, participated in the study. Assessment of serum total bilirubin, alanine and aspartate aminotransferase, muscle strength, body composition, and 6-minute walk test (6MWT) were performed before treatment and 12 weeks after the end of the treatment period. RESULTS In the 6MWT test we observed significant subjective (dyspnea: 58.3% pretreatment vs 27.6% posttreatment, P = .018; fatigue: 96.6% pretreatment vs 51.7% posttreatment, P = .0001) and objective improvement (distance: 415.4 meters pretreatment vs 505.2 meters posttreatment, P < .0000001). We did not observe an increase in muscle mass nor improvement in blood biochemical parameters. CONCLUSION A significant objective and subjective improvement in physical performance was seen in liver transplant recipients after successful treatment of HCV infection with DAA.
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Affiliation(s)
- M Wojtowicz
- Department of Immunology, Transplant Medicine and Internal Diseases, Medical University of Warsaw, Warsaw, Poland
| | - P Wilkowski
- Department of Immunology, Transplant Medicine and Internal Diseases, Medical University of Warsaw, Warsaw, Poland
| | - E Hryniewiecka
- Department of Immunology, Transplant Medicine and Internal Diseases, Medical University of Warsaw, Warsaw, Poland; Department of Clinical Nursing, Medical University of Warsaw, Warsaw, Poland
| | - T Cieciura
- Department of Immunology, Transplant Medicine and Internal Diseases, Medical University of Warsaw, Warsaw, Poland
| | - L Paczek
- Department of Immunology, Transplant Medicine and Internal Diseases, Medical University of Warsaw, Warsaw, Poland; Department of Bioinformatics, Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Warsaw, Poland
| | - M Ciszek
- Department of Immunology, Transplant Medicine and Internal Diseases, Medical University of Warsaw, Warsaw, Poland.
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Mapoure NY, Budzi MN, Eloumou SAFB, Malongue A, Okalla C, Luma HN. Neurological manifestations in chronic hepatitis C patients receiving care in a reference hospital in sub-Saharan Africa: A cross-sectional study. PLoS One 2018; 13:e0192406. [PMID: 29513678 PMCID: PMC5841655 DOI: 10.1371/journal.pone.0192406] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2017] [Accepted: 01/22/2018] [Indexed: 01/11/2023] Open
Abstract
BACKGROUND Chronic hepatitis C infection is a major public health concern, with a high burden in Sub-Saharan Africa. There is growing evidence that chronic hepatitis C virus (HCV) infection causes neurological complications. This study aimed at assessing the prevalence and factors associated with neurological manifestations in chronic hepatitis C patients. METHODS Through a cross-sectional design, a semi-structured questionnaire was used to collect data from consecutive chronic HCV infected patients attending the outpatient gastroenterology unit of the Douala General Hospital (DGH). Data collection was by interview, patient record review (including HCV RNA quantification, HCV genotyping and the assessment of liver fibrosis and necroinflammatory activity), clinical examination complemented by 3 tools; Neuropathic pain diagnostic questionnaire, Brief peripheral neuropathy screen and mini mental state examination score. Data were analysed using Statistical package for social sciences version 20 for windows. RESULTS Of the 121 chronic hepatitis C patients (51.2% males) recruited, 54.5% (95% Confidence interval: 46.3%, 62.8%) had at least one neurological manifestation, with peripheral nervous system manifestations being more common (50.4%). Age ≥ 55 years (Adjusted Odds Ratio: 4.82, 95%CI: 1.02-18.81, p = 0.02), longer duration of illness (AOR: 1.012, 95%CI: 1.00-1.02, p = 0.01) and high viral load (AOR: 3.40, 95% CI: 1.20-9.64, p = 0.02) were significantly associated with neurological manifestations. Peripheral neuropathy was the most common neurological manifestation (49.6%), presenting mainly as sensory neuropathy (47.9%). Age ≥ 55 years (AOR: 6.25, 95%CI: 1.33-29.08, p = 0.02) and longer duration of illness (AOR: 1.01, 1.00-1.02, p = 0.01) were significantly associated with peripheral neuropathy. CONCLUSION Over half of the patients with chronic hepatitis C attending the DGH have a neurological manifestation, mainly presenting as sensory peripheral neuropathy. Routine screening of chronic hepatitis C patients for peripheral neuropathy is therefore necessary, with prime focus on those with older age and longer duration of illness.
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Affiliation(s)
- N. Y. Mapoure
- Department of Clinical Sciences, Faculty of Medicine and Pharmaceutical Sciences, University of Douala, Douala, Cameroon
- Department of Internal Medicine, Douala General Hospital, Douala, Cameroon
| | - M. N. Budzi
- Faculty of Health Sciences, University of Buea, Buea, Cameroon
| | - S. A. F. B. Eloumou
- Department of Clinical Sciences, Faculty of Medicine and Pharmaceutical Sciences, University of Douala, Douala, Cameroon
- Department of Internal Medicine, Douala General Hospital, Douala, Cameroon
| | - A. Malongue
- Department of Internal Medicine, Douala General Hospital, Douala, Cameroon
| | - C. Okalla
- Department of Internal Medicine, Douala General Hospital, Douala, Cameroon
- Department of Biological Sciences, Faculty of Medicine and Pharmaceutical Sciences, University of Douala, Douala, Cameroon
| | - H. N. Luma
- Department of Internal Medicine, Douala General Hospital, Douala, Cameroon
- Department of Internal Medicine, Faculty of Medicine and Biomedical Sciences, University of Yaoundé I, Yaounde, Cameroon
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Retamozo S, Brito-Zerón P, Quartuccio L, De Vita S, Ramos-Casals M. Introducing treat-to-target strategies of autoimmune extrahepatic manifestations of chronic hepatitis C virus infection. Expert Rev Clin Pharmacol 2017; 10:1085-1101. [PMID: 28715943 DOI: 10.1080/17512433.2017.1357466] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
INTRODUCTION The hepatitis C virus (HCV) is recognized as one of the hepatic viruses most often associated with extrahepatic manifestations (EHMs). It is currently accepted that cryoglobulinemic vasculitis (CV) is the key autoimmune extrahepatic disease associated with HCV infection. Therapeutic approaches have mainly been based on the use of old antiviral interferon (IFN)-based regimens and immunosuppressive therapies, often with an inadequate balance between therapeutic benefits and excess side effects. Areas covered: Therapeutic management of HCV patients with EHMs, including both non-autoimmune (cardiovascular, hematological, general features) and autoimmune complications (organ-specific and systemic autoimmune diseases). Therapies included antiviral (IFN, ribavirin, direct-acting antivirals - DAAs-) and non-antiviral (immunosuppressive agents, rituximab, plasma exchanges) options. The review analyses the current evidence for proposing a treat-to-target (T2T) approach for HCV-related autoimmune EHMs based on an organ-by-organ strategy. Expert commentary: Eradication of HCV must be considered the key T2T in the therapeutic approach to HCV-related EHMs, as there has been a disruptive change due to the appearance of direct-acting antivirals (DAAs) as game-changers in HCV therapy, with an efficacy reaching nearly 100%. In this scenario, the central role played until now by IFN and ribavirin is not currently supported and they will not be used in the future.
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Affiliation(s)
- Soledad Retamozo
- a Hospital Privado Universitario de Córdoba , Instituto Universitario para las Ciencias Biomédicas de Córdoba (IUCBC) , Córdoba , Argentina.,b Laboratory of Autoimmune Diseases Josep Font , IDIBAPS-CELLEX , Barcelona , Spain.,g Instituto De Investigaciones En Ciencias De La Salud (INICSA) , Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET) , Córdoba , Argentina
| | - Pilar Brito-Zerón
- b Laboratory of Autoimmune Diseases Josep Font , IDIBAPS-CELLEX , Barcelona , Spain.,c Autoimmune Diseases Unit, Department of Medicine , Hospital CIMA- Sanitas , Barcelona , Spain.,d Department of Autoimmune Diseases, ICMiD , Hospital Clínic , Barcelona , Spain
| | - Luca Quartuccio
- e Rheumatology Clinic, Department of Medical and Biological Sciences, Azienda Ospedaliero Universitaria S. Maria della Misericordia , University of Udine , Udine , Italy
| | - Salvatore De Vita
- e Rheumatology Clinic, Department of Medical and Biological Sciences, Azienda Ospedaliero Universitaria S. Maria della Misericordia , University of Udine , Udine , Italy
| | - Manuel Ramos-Casals
- b Laboratory of Autoimmune Diseases Josep Font , IDIBAPS-CELLEX , Barcelona , Spain.,d Department of Autoimmune Diseases, ICMiD , Hospital Clínic , Barcelona , Spain.,f Department of Medicine , University of Barcelona , Barcelona , Spain
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Refractory Mononeuritis Multiplex Due to Hepatitis C Infection and Cryoglobulinemia: Efficient Response to Rituximab. Neurologist 2017; 21:47-8. [PMID: 27119277 DOI: 10.1097/nrl.0000000000000075] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
BACKGROUND Mononeuritis multiplex due to hepatitis C infection and cryoglobulinemia has no specific treatment guidelines. Despite the favorable evolution of the liver disease after treatment with interferon and ribavirin, neurological symptoms might not respond very efficiently to antiviral therapy. CASE REPORT We report the case of a 50-year-old woman, with a mononeuritis multiplex related to cryoglobulinemia and hepatitis C virus infection, who was treated with rituximab. Hepatitis C virus infection was treated successfully with interferon-α and ribavirin, but the neurological symptoms were still worsening until rituximab therapy. Significant improvement of paraparesis and painful hypoesthesia were evident after the fourth infusion of rituximab. However, every 6 months, the neurological symptoms relapsed and the patient was subjected to a new cycle of rituximab therapy, with the disappearing of the paraparesis and hypoesthesias. CONCLUSIONS This case highlights the potential use of rituximab in immune-mediated neuropathies, especially the mononeuritis multiplex associated with hepatitis C infection.
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Mathew S, Faheem M, Ibrahim SM, Iqbal W, Rauff B, Fatima K, Qadri I. Hepatitis C virus and neurological damage. World J Hepatol 2016; 8:545-556. [PMID: 27134702 PMCID: PMC4840160 DOI: 10.4254/wjh.v8.i12.545] [Citation(s) in RCA: 46] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/27/2015] [Revised: 03/19/2016] [Accepted: 04/07/2016] [Indexed: 02/06/2023] Open
Abstract
Chronic hepatitis C virus (HCV) infection exhibits a wide range of extrahepatic complications, affecting various organs in the human body. Numerous HCV patients suffer neurological manifestations, ranging from cognitive impairment to peripheral neuropathy. Overexpression of the host immune response leads to the production of immune complexes, cryoglobulins, as well as autoantibodies, which is a major pathogenic mechanism responsible for nervous system dysfunction. Alternatively circulating inflammatory cytokines and chemokines and HCV replication in neurons is another factor that severely affects the nervous system. Furthermore, HCV infection causes both sensory and motor peripheral neuropathy in the mixed cryoglobulinemia as well as known as an important risk aspect for stroke. These extrahepatic manifestations are the reason behind underlying hepatic encephalopathy and chronic liver disease. The brain is an apt location for HCV replication, where the HCV virus may directly wield neurotoxicity. Other mechanisms that takes place by chronic HCV infection due the pathogenesis of neuropsychiatric disorders includes derangement of metabolic pathways of infected cells, autoimmune disorders, systemic or cerebral inflammation and alterations in neurotransmitter circuits. HCV and its pathogenic role is suggested by enhancement of psychiatric and neurological symptoms in patients attaining a sustained virologic response followed by treatment with interferon; however, further studies are required to fully assess the impact of HCV infection and its specific antiviral targets associated with neuropsychiatric disorders.
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Affiliation(s)
- Shilu Mathew
- Shilu Mathew, Muhammed Faheem, Center of Excellence in Genomic Medicine Research, King Abdulaziz University, Jeddah 21589, Saudi Arabia
| | - Muhammed Faheem
- Shilu Mathew, Muhammed Faheem, Center of Excellence in Genomic Medicine Research, King Abdulaziz University, Jeddah 21589, Saudi Arabia
| | - Sara M Ibrahim
- Shilu Mathew, Muhammed Faheem, Center of Excellence in Genomic Medicine Research, King Abdulaziz University, Jeddah 21589, Saudi Arabia
| | - Waqas Iqbal
- Shilu Mathew, Muhammed Faheem, Center of Excellence in Genomic Medicine Research, King Abdulaziz University, Jeddah 21589, Saudi Arabia
| | - Bisma Rauff
- Shilu Mathew, Muhammed Faheem, Center of Excellence in Genomic Medicine Research, King Abdulaziz University, Jeddah 21589, Saudi Arabia
| | - Kaneez Fatima
- Shilu Mathew, Muhammed Faheem, Center of Excellence in Genomic Medicine Research, King Abdulaziz University, Jeddah 21589, Saudi Arabia
| | - Ishtiaq Qadri
- Shilu Mathew, Muhammed Faheem, Center of Excellence in Genomic Medicine Research, King Abdulaziz University, Jeddah 21589, Saudi Arabia
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Cashman CR, Höke A. Mechanisms of distal axonal degeneration in peripheral neuropathies. Neurosci Lett 2015; 596:33-50. [PMID: 25617478 PMCID: PMC4428955 DOI: 10.1016/j.neulet.2015.01.048] [Citation(s) in RCA: 154] [Impact Index Per Article: 15.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2014] [Revised: 01/16/2015] [Accepted: 01/19/2015] [Indexed: 02/08/2023]
Abstract
Peripheral neuropathy is a common complication of a variety of diseases and treatments, including diabetes, cancer chemotherapy, and infectious causes (HIV, hepatitis C, and Campylobacter jejuni). Despite the fundamental difference between these insults, peripheral neuropathy develops as a combination of just six primary mechanisms: altered metabolism, covalent modification, altered organelle function and reactive oxygen species formation, altered intracellular and inflammatory signaling, slowed axonal transport, and altered ion channel dynamics and expression. All of these pathways converge to lead to axon dysfunction and symptoms of neuropathy. The detailed mechanisms of axon degeneration itself have begun to be elucidated with studies of animal models with altered degeneration kinetics, including the slowed Wallerian degeneration (Wld(S)) and Sarm knockout animal models. These studies have shown axonal degeneration to occur through a programmed pathway of injury signaling and cytoskeletal degradation. Insights into the common disease insults that converge on the axonal degeneration pathway promise to facilitate the development of therapeutics that may be effective against other mechanisms of neurodegeneration.
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Affiliation(s)
- Christopher R Cashman
- Departments of Neuroscience and Neurology, USA; MSTP- MD/PhD Program, Johns Hopkins University, Baltimore, MD 21205, USA
| | - Ahmet Höke
- Departments of Neuroscience and Neurology, USA.
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Kuate-Tegueu C, Temfack E, Ngankou S, Doumbe J, Djientcheu VP, Kengne AP. Prevalence and determinants of diabetic polyneuropathy in a sub-Saharan African referral hospital. J Neurol Sci 2015; 355:108-12. [PMID: 26048049 DOI: 10.1016/j.jns.2015.05.035] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2015] [Revised: 05/02/2015] [Accepted: 05/25/2015] [Indexed: 11/25/2022]
Abstract
BACKGROUND Diabetic peripheral neuropathy is the commonest complication of diabetes mellitus, and a major cause of limb amputations. In general however, the magnitude of diabetic neuropathy in sub-Saharan Africans with diabetes has been less reliably quantified. We assessed the prevalence and determinants of diabetic polyneuropathy in hospital settings in Cameroon. METHODS We conducted a cross-sectional survey at the Douala Laquintinie Hospital, which is one of the main reference hospital in the economic capital of Cameroon (3 million populations). Participants included all patients with type 1 (T1DM) or type 2 (T2DM) diabetes who reported to the hospital regardless of the reason, during a 5-month recruitment period. Polyneuropathy was defined as diabetic in a patient with a Diabetic Neuropathy Examination score of >3/16 and/or a monofilament score of <5/9. RESULTS A total of 306 patients were recruited, including 196 women (64%) and 294 (96%) with T2DM. The mean (standard deviation) values were 59.8 (11.2) years for age and 8.4 (8.2) years for diabetes duration. Clinical signs of polyneuropathy were present in 102 (crude prevalence rate: 33.3%) patients. The polyneuropathy was symptomatic in 79/102 (77.4%) patients. Determinants of polyneuropathy were urban residence (p=0.02), infection with hepatitis C virus (p=0.002), infection with HIV (p=0.012) and presence of albuminuria (p=0.0001). CONCLUSION About one in three patients with diabetes reporting to the hospital in our setting has prevalent diabetes related polyneuropathy. This emphasizes the importance of routine implementation of therapeutic education and other measures to limit the complications.
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Affiliation(s)
- C Kuate-Tegueu
- Faculty of Medicine and Biomedical Sciences, University of Yaounde 1, Cameroon; Neurology Department, Douala Laquintinie Hospital, Cameroon.
| | - E Temfack
- Department of Internal Medicine, Douala General Hospital, Cameroon
| | - S Ngankou
- Neurology Department, Douala Laquintinie Hospital, Cameroon
| | - J Doumbe
- Neurology Department, Douala Laquintinie Hospital, Cameroon; Faculty of Medicine and Pharmaceutical Sciences, University of Douala, Cameroon
| | - V P Djientcheu
- Faculty of Medicine and Biomedical Sciences, University of Yaounde 1, Cameroon
| | - A P Kengne
- South African Medical Research Council & University of Cape Town
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Benstead TJ, Chalk CH, Parks NE. Treatment for cryoglobulinemic and non-cryoglobulinemic peripheral neuropathy associated with hepatitis C virus infection. Cochrane Database Syst Rev 2014; 2014:CD010404. [PMID: 25525951 PMCID: PMC11232532 DOI: 10.1002/14651858.cd010404.pub2] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/29/2023]
Abstract
BACKGROUND Peripheral neuropathy is the most common neurologic complication of hepatitis C virus (HCV) infection. The pathophysiology of the neuropathy associated with HCV is not definitively known; however, proposed mechanisms include cryoglobulin deposition in the vasa nervorum and HCV-mediated vasculitis. The optimal treatment for HCV-related peripheral neuropathy has not been established. OBJECTIVES To assess the effects of interventions (including interferon alfa, interferon alfa plus ribavirin, corticosteroids, cyclophosphamide, plasma exchange, and rituximab) for cryoglobulinemic or non-cryoglobulinemic peripheral neuropathy associated with HCV infection. SEARCH METHODS On 26 August 2014, we searched the Cochrane Neuromuscular Disease Group Specialized Register, CENTRAL, MEDLINE, and EMBASE. We also searched two trials registers, the Networked Digital Library of Theses and Dissertations (NDLTD) (October 2014), and three other databases. We checked references in identified trials and requested information from trial authors to identify any additional published or unpublished data. SELECTION CRITERIA We included all randomized controlled trials (RCTs) and quasi-RCTs involving participants with cryoglobulinemic or non-cryoglobulinemic peripheral neuropathy associated with HCV infection. We considered any intervention (including interferon alfa, interferon alfa plus ribavirin, corticosteroids, cyclophosphamide, plasma exchange, and rituximab) alone or in combination versus placebo or another intervention ('head-to-head' comparison study design) evaluated after a minimum interval to follow-up of at least six months. DATA COLLECTION AND ANALYSIS We used standard methodological procedures expected by The Cochrane Collaboration. The planned primary outcome was change in sensory impairment (using any validated sensory neuropathy scale or quantitative sensory testing) at the end of the follow-up period. Other planned outcomes were: change in impairment (any validated combined sensory and motor neuropathy scale), change in disability (any validated disability scale), electrodiagnostic measures, number of participants with improved symptoms of neuropathy (global impression of change), and severe adverse events. MAIN RESULTS Four trials of HCV-related cryoglobulinemia fulfiled selection criteria and the review authors included three in quantitative synthesis. All studies were at high risk of bias. No trial addressed the primary outcome of change in sensory impairment. No trial addressed secondary outcomes of change in combined sensory and motor impairment, disability, or electrodiagnostic measures. A single trial of HCV-related mixed cryoglobulinemia treated with pegylated interferon alfa (peginterferon alfa), ribavirin, and rituximab versus peginterferon alfa and ribavirin did not show a significant difference in the number of participants with improvement in neuropathy at 36 months post treatment (risk ratio (RR) 4.00, 95% confidence interval (CI) 0.27 to 59.31, n = 9). One study of interferon alfa (n = 22) and two studies of rituximab (n = 61) provided adverse event data. Severe adverse events were no more common with interferon alfa (RR 7.00, 95% CI 0.38 to 128.02) or rituximab (RR 3.00, 95% CI 0.13 to 67.06) compared to the control group. AUTHORS' CONCLUSIONS There is a lack of RCTs and quasi-RCTs addressing the effects of interventions for peripheral neuropathy associated with HCV infection. At present, there is insufficient evidence from RCTs and quasi-RCTs to make evidence-based decisions about treatment.
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Affiliation(s)
- Tim J Benstead
- Department ofMedicine,Division ofNeurology,DalhousieUniversity, Room3828Halifax Infirmary, 1796 Summer Street, Halifax, NS, B3H 3A7, Canada.
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Jain J, Singh R, Banait S, Verma N, Waghmare S. Magnitude of peripheral neuropathy in cirrhosis of liver patients from central rural India. Ann Indian Acad Neurol 2014; 17:409-15. [PMID: 25506162 PMCID: PMC4251014 DOI: 10.4103/0972-2327.144012] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2014] [Revised: 03/05/2014] [Accepted: 05/08/2014] [Indexed: 12/12/2022] Open
Abstract
Context: Cirrhosis of liver is an important cause of morbidity and mortality and if associated with peripheral neuropathy (PN) it also poses a huge financial, psychological burden for the patients and their families. Aim: The aim of the present study was to study the magnitude of PN among subjects with cirrhosis of liver presenting to tertiary care teaching hospital in central rural India. Settings and Design: A cross-sectional study was performed in a tertiary care teaching hospital. Materials and Methods: In all patients of cirrhosis of liver irrespective of etiology, aged 15 and above, undergone clinical assessment for peripheral nervous systems damage and confirmed by nerve conduction studies. Statistical Analysis Used: We used chi square test to study associations. P value ≤0.05 was considered as significant. Crude odds ratios were computed to assess the strength of association between independent variables and dependent variables along with their 95% confidence intervals. Results: We included 207 of cirrhosis of liver patients admitted in medicine department from November 2010 through November 2013. Nearly 83% patients were male and 63.2% patients were under the age of 45 years. Common features in these patients were ascites (71%) splenomegaly (63.3%) pedal edema (61.4%) icterus (46.4%) tingling (44.9%) gastrointestinal bleeding(39.1%), ataxia (26.6%), numbness(26.6%), distal motor weakness (21.7%) and paresthesia(20.8%). Among the manifestation of peripheral nerve involvement, loss of ankle reflex was the most common feature in 51.7%, followed by loss of temperature sense 29.5%, loss of vibration sense 20.8%, loss of touch 16.4%, loss of position sense 14.5% and loss of pain in 6.3% of the patients. Peripheral neuropathy was found in 53.6% [95% CI: 46.58- 60.56] study subjects on electrophysiological study. Conclusions: Analysis of electrophysiological study shows that the PN is very common in study subjects with cirrhosis of liver, especially in male subjects, during the middle age group.
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Affiliation(s)
- Jyoti Jain
- Department of Medicine, Mahatma Gandhi Institute of Medical Sciences, Sevagram, Wardha, Maharashtra, India
| | - Ramji Singh
- Department of Physiology, All India Institute of Medical Sciences, Patna, Bihar, India
| | - Shashank Banait
- Department of Ophthalmology, Jawaharlal Nehru Medical College, Sawangi Meghe, Wardha, Maharashtra, India
| | - Nitin Verma
- Department of Physiology, Mahatma Gandhi Institute of Medical Sciences, Sevagram, Wardha, Maharashtra, India
| | - Satish Waghmare
- Department of Physiology, Mahatma Gandhi Institute of Medical Sciences, Sevagram, Wardha, Maharashtra, India
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Biasiotta A, Casato M, La Cesa S, Colantuono S, Di Stefano G, Leone C, Carlesimo M, Piroso S, Cruccu G, Truini A. Clinical, neurophysiological, and skin biopsy findings in peripheral neuropathy associated with hepatitis C virus-related cryoglobulinemia. J Neurol 2014; 261:725-31. [PMID: 24500496 DOI: 10.1007/s00415-014-7261-7] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2013] [Revised: 01/21/2014] [Accepted: 01/22/2014] [Indexed: 01/14/2023]
Abstract
Hepatitis C virus (HCV)-related cryoglobulinemia commonly causes disabling complications including peripheral neuropathy and neuropathic pain. In this prospective clinical, neurophysiological, and skin biopsy study we aimed at assessing clinical characteristics and risk factors of peripheral neuropathy and neuropathic pain in patients with HCV-related cryoglobulinemia. We enrolled 69 consecutive patients with HCV-related cryoglobulinemia. We diagnosed neuropathic pain with the DN4 (Neuropathic Pain Diagnostic) questionnaire, and rated the various neuropathic pains with the Neuropathic Pain Symptom Inventory (NPSI). All patients underwent a standard nerve conduction study to assess Aβ-fiber function, laser-evoked potentials to assess Aδ-fiber function, and skin biopsy to assess C-fiber terminals. Of the 69 patients studied, 47 had a peripheral neuropathy, and 29 had neuropathic pain. Patients with peripheral neuropathy were older than those without (P < 0.0001). While peripheral neuropathy was significantly associated with the duration of HCV infection (P < 0.01), it was unrelated to the duration of cryoglobulinemia and cryocrit (P > 0.5). The severity of peripheral neuropathy significantly correlated with the duration of HCV infection (P < 0.05). Laser-evoked potential amplitudes were significantly lower in patients with than in those without neuropathic pain (P < 0.05). Conversely, no difference was found in nerve conduction study and skin biopsy findings (P > 0.05). Our findings show that peripheral neuropathy is related to age and HCV infection, rather than to cryoglobulinemia, and neuropathic pain is associated with damage to nociceptive pathways as assessed with laser-evoked potentials; this might be useful for designing more effective clinical interventions for these common HCV related-cryoglobulinemia complications.
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Affiliation(s)
- A Biasiotta
- Department of Neurology and Psychiatry, Sapienza University, Viale Università 30, 00185, Rome, Italy
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Rosati M, Andreani L, Poggetti A, Zampa V, Parchi P, Lisanti M. Progressive Brachial Plexus Palsy after Osteosynthesis of an Inveterate Clavicular Fracture. J Orthop Case Rep 2013; 3:18-21. [PMID: 27298912 PMCID: PMC4719249 DOI: 10.13107/jocr.2250-0685.109] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022] Open
Abstract
INTRODUCTION The thoracic outlet syndrome (TOS) is a rare complication of clavicular fracture, occurring in 0.5-9% of cases. In the literature from 1965 - 2010, 425 cases of TOS complicating a claviclular fracture were described. However, only 5 were observed after a surgical procedure of reduction and fixation. The causes of this complication were due to the presence of an exuberant callus, to technical surgery errors or to vascular lesions. In this paper we describe a case of brachial plexus plasy after osteosynthesis of clavicle fracture. CASE REPORT A 48 year old female, presented to us with inveterate middle third clavicle fracture of 2 months duration. She was an alcoholic, smoker with an history of opiate abuse and was HCV positive. At two month the fracture was displaced with no signs of union and open rigid fixation with plate was done. The immediate postoperative patient had signs of neurologic injury. Five days after surgery showed paralysis of the ulnar nerve, at 10 days paralysis of the median nerve, radial and ulnar paresthesias in the territory of the C5-C6-C7-C8 roots. She was treated with rest, steroids and neurotrophic drugs. One month after surgery the patient had signs of complete denervation around the brachial plexus. Implant removal was done and in a month ulnar and median nerve functions recovered. At three months post implant removal the neurological picture returned to normal. CONCLUSION We can say that TOS can be seen as arising secondary to an "iatrogenic compartment syndrome" justified by the particular anatomy of the space cost joint. The appropriateness of the intervention for removal of fixation devices is demonstrated by the fact that the patient has returned to her daily activities in the absence of symptoms and good functional recovery in about three months, despite fracture nonunion.
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Affiliation(s)
- Marco Rosati
- Orthopaedic and Traumatology I Department, University of Pisa
| | | | - Andrea Poggetti
- Orthopaedic and Traumatology I Department, University of Pisa
| | - Virna Zampa
- Orthopaedic and Traumatology I Department, University of Pisa
- Diagnostic I Department, University of Pisa
| | - Paolo Parchi
- Orthopaedic and Traumatology I Department, University of Pisa
| | - Michele Lisanti
- Orthopaedic and Traumatology I Department, University of Pisa
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Benstead TJ, Chalk CH, Parks NE. Treatment for cryoglobulinemic and non-cryoglobulinemic peripheral neuropathy associated with hepatitis C virus infection. THE COCHRANE DATABASE OF SYSTEMATIC REVIEWS 2013. [DOI: 10.1002/14651858.cd010404] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
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Abstract
PURPOSE OF REVIEW Vasculitic neuropathy is a heterogeneous disorder that usually occurs in systemic diseases, but less commonly appears as nonsystemic vasculitic neuropathy (NSVN). This review is intended to highlight recent developments in the field of vasculitic neuropathies. RECENT FINDINGS A Peripheral Nerve Society guideline provides data-driven consensus recommendation on classification of vasculitic neuropathies and diagnosis/treatment of NSVN. NSVN is sometimes accompanied by subclinical inflammation of adjacent skin. Amyotrophic lateral sclerosis with sensory involvement can mimic NSVN. Systemic vasculitides with neuropathy include polyarteritis nodosa, microscopic polyangiitis (MPA), rheumatoid vasculitis, Churg-Strauss syndrome (CSS), and hepatitis C-related mixed cryoglobulinemic vasculitis (MCV). At autopsy, MPA affects limb nerves diffusely, with maximal damage in proximal/middle segments. CSS can be accompanied by antineutrophil cytoplasmic antibodies (ANCAs), but most patients with neuropathy lack ANCAs. Cryoglobulinemic neuropathies are usually caused by vasculitis, irrespective of phenotype. Two randomized trials revealed rituximab to be noninferior to cyclophosphamide for inducing remission in ANCA-associated vasculitis. Many reports also document efficacy of rituximab in MCV. SUMMARY Consensus guidelines on NSVN should be evaluated prospectively. MPA-associated vasculitic neuropathy results from vasculitic lesions distributed diffusely throughout peripheral extremity nerves. Rituximab is effective for ANCA-associated and cryoglobulinemic vasculitis with neuropathy.
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Abstract
Hepatitis C virus (HCV) infection is a growing international health problem, and more than 170 million people are chronic carriers. Up to 50% of HCV-positive patients develop at least one extrahepatic manifestation during the course of disease. To varying degrees of certainty, there is evidence of an association between chronic HCV infection and a variety of neuromuscular diseases. The pathogenesis of most extrahepatic diseases remains unclear but possibly includes HCV lymphotropism and/or HCV-induced autoantibodies. The therapeutic approach to HCV-associated autoimmune disorders entails eradication of HCV with one of the recombinant interferon-alpha preparations with or without additional immunosuppressive drugs.
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McCarthy M, Ortega MR. Neurological complications of hepatitis C infection. Curr Neurol Neurosci Rep 2012; 12:642-54. [PMID: 22991069 DOI: 10.1007/s11910-012-0311-6] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Though well-known as a cause of liver disease, Hepatitis C virus infection is emerging as a cause of a variety of peripheral and central nervous system disorders. The virus causes chronic persistent infection with complex immune responses in the majority of individuals. Viral infection may have the potential to generate neurological illness through direct infection of neural cells or through immune-mediated mechanisms, including enhancement of autoimmune responses. Moreover, the mainstay of antiviral treatment of hepatitis C infection, interferon-alpha, is itself associated with neurological morbidity. Thus neurologists are increasingly faced with diagnosing or even predicting a wide spectrum of neurological complications of hepatitis C infection and/or its treatment.
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Affiliation(s)
- Micheline McCarthy
- Neurology (127), Bruce Carter Veterans Affairs Medical Center, 1201 NW 16th Street, Miami, FL 33125, USA.
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Abstract
The primary hepatotropic viruses are associated with various extrahepatic manifestations including peripheral nervous system disorders. The pathogenesis of these complications is not clear-cut. Patients with confirmed liver damage coexisting with peripheral nervous system manifestations, especially Guillain-Barré syndrome, mononeuropathy, mononeuropathy multiplex and polyneuropathy should be screened for the viral hepatitis in the differential diagnosis. There are no defined strategies of treatment for these manifestations, so the therapy should be individualized. The purpose of this review is to discuss the etiology, pathogenesis and treatment of the neuropathies in the course of primary hepatotropic viral infections such as hepatitis A, B, C and E viruses.
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Abstract
Cryoglobulins are immunoglobulins that precipitate in vitro at temperatures less than 37°C and produce organ damage through two main pathways: vascular sludging (hyperviscosity syndrome, mainly in type I cryoglobulinaemia) and immune-mediated mechanisms (principally vasculitis, in mixed cryoglobulinaemia). Cryoglobulinaemia is associated with many illnesses, which can be broadly grouped into infections, autoimmune disorders, and malignancies; the most common cause is infection with hepatitis C virus. Mixed cryoglobulinaemic syndrome is diagnosed when a patient has typical organ involvement (mainly skin, kidney, or peripheral nerve) and circulating cryoglobulins. Cutaneous purpura is the most common manifestation of cryoglobulinaemic vasculitis. The most frequently affected internal organs are the peripheral nerves, kidneys, and joints. The course varies widely and prognosis is influenced by both cryoglobulinaemic damage to vital organs and by comorbidities associated with underlying diseases. More than 90% of cases of cryoglobulinaemia have a known underlying cause; therefore treatment is focused on the cause of the disorder rather than merely symptomatic relief. Studies suggest that both combined or sequential antiviral therapies and targeted biological treatments might be more effective than monotherapy.
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Affiliation(s)
- Manuel Ramos-Casals
- Josep Font Laboratory of Autoimmune Diseases, Institut Clínic de Medicina I Dermatologia, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer, University of Barcelona, Barcelona, Spain
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Hubbard JJ, Kottilil S. Extra-hepatic replication of the hepatitis C virus: current issues and future directions. Future Virol 2011. [DOI: 10.2217/fvl.11.7] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Affiliation(s)
- Jonathan J Hubbard
- Immunopathogenesis Section, Laboratory of Immunoregulation, National institute of Allergy & Infectious Diseases, National Institutes of Health, Department of Health & Human Sciences, Bldg 10, Room 11N204, 9000 Rockville Pike, Bethesda, MD 20892, USA
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Abstract
Infection with hepatitis C virus (HCV) can be associated with demyelinating polyneuropathy that may be responsive to immunomodulatory therapy. In this case report series, we review four patients (all male, ages 47-60 years) with HCV and demyelinating polyneuropathy. Two of the four patients were diagnosed with HCV during the course of initial neuropathy evaluation. All patients had sensory loss, absent/diminished reflexes, lower extremity weakness (except for one patient), and demyelinating electrodiagnostic features. Three patients had polyclonal hypergammaglobulinemia and one patient had IgM monoclonal gammopathy. Intravenous immunoglobulin resulted in improvement in three patients; one patient had no benefit from rituximab therapy, but his symptoms have been stable. Demyelinating neuropathy may develop in patients with HCV unrelated to antiviral therapy. Immunomodulatory therapy may be beneficial in some cases. Testing for HCV should be considered, especially in patients with hypergammaglobulinemia or IgM monoclonal gammopathy.
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Yoon MS, Obermann M, Dockweiler C, Assert R, Canbay A, Haag S, Gerken G, Diener HC, Katsarava Z. Sensory neuropathy in patients with cryoglobulin negative hepatitis-C infection. J Neurol 2010; 258:80-8. [PMID: 20683606 DOI: 10.1007/s00415-010-5686-1] [Citation(s) in RCA: 28] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2010] [Revised: 07/15/2010] [Accepted: 07/20/2010] [Indexed: 12/15/2022]
Abstract
There is growing evidence that hepatitis-C virus (HCV) infection might cause peripheral neuropathy. We aimed to investigate the prevalence, clinical and electrophysiological features of sensory neuropathy in patients with cryoglobulin negative HCV infection. We studied 46 consecutive cryoglobulin negative HCV positive patients (24 of them with and 22 without neuropathic symptoms, NS) and compared to 28 age and gender matched controls. In all patients and controls, clinical neuropathy symptom (NSS) and neuropathy deficit scores (NDS) were assessed and standard nerve conduction velocity (SNCV) and pain related-evoked potentials (PREP) were recorded. Both, SNCV and PREP were abnormal in 13 NS positive patients (13/46, 28%). Abnormal PREP but normal SNCV were found in 5 (5/46, 11%) NS positive and in 2 NS negative patients (2/46, 4%). PREP abnormalities correlated positive with both clinical neuropathy scores (NSS r=0.62; p<0.001; NDS r=0.57; p<0.001), but not with the duration of the disease, current viral load, or the virus subtype. PREP abnormalities were more frequent (16/33, 48.5%) in HCV patients treated with interferon than in therapy naïve patients (4/13, 30.8%); the difference was, however, not significant. In our present study (1) all virus subtypes are capable of inducing neuropathy, (2) no differences were found between interferon therapy and treatment naive patients, (3) the prevalence of peripheral sensory neuropathy including small sensory fibers (20/46, 43.5%) is higher than previously reported and (4) we found that detection of HCV associated neuropathy depends on the evaluation method.
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Affiliation(s)
- Min-Suk Yoon
- Department of Neurology, University of Duisburg-Essen, Hufelandstrasse 55, 45122, Essen, Germany.
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Cherry CL, Affandi JS, Brew BJ, Creighton J, Djauzi S, Hooker DJ, Imran D, Kamarulzaman A, Kamerman P, McArthur JC, Moore RD, Price P, Smyth K, Tan IL, Vanar S, Wadley A, Wesselingh SL, Yunihastuti E. Hepatitis C seropositivity is not a risk factor for sensory neuropathy among patients with HIV. Neurology 2010; 74:1538-42. [PMID: 20458071 DOI: 10.1212/wnl.0b013e3181dd436d] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023] Open
Abstract
BACKGROUND Sensory neuropathy (SN) is common in patients with HIV. Hepatitis C (HCV) coinfection is often cited as an HIV-SN risk factor, but data to support this are lacking. This collaboration aimed to examine the association between HCV serostatus and SN risk among ambulatory HIV-positive patients. METHODS Patients with HIV were assessed in cross-sectional studies in Baltimore, Jakarta, Johannesburg, Kuala Lumpur, Melbourne, and Sydney for SN (defined by both supportive symptoms and signs). HCV seropositivity was assessed as an SN risk using a chi(2) test, followed by logistic regression modeling to correct for treatment exposures and demographics. RESULTS A total of 837 patients of African, Asian, and Caucasian descent were studied. HCV seroprevalence varied by site (Baltimore n = 104, 61% HCV+; Jakarta 96, 51%; Johannesburg 300, 1%; Kuala Lumpur 97, 10%; Melbourne 206, 16%; Sydney 34, 18%). HCV seropositivity was not associated with increased SN risk at any site, but was associated with reduced SN risk in Melbourne (p = 0.003). On multivariate analyses, the independent associations with SN were increasing age, height, and stavudine exposure. HCV seropositivity was not independently associated with an increased SN risk at any site, but associated independently with reduced SN risk in Baltimore (p = 0.04) and Melbourne (p = 0.06). CONCLUSIONS Hepatitis C (HCV) seropositivity was not associated with increased sensory neuropathy risk among HIV-positive patients at any site. While we were unable to assess HCV RNA or liver damage, the data suggest that HCV coinfection is not a major contributor to HIV-SN. HCV = hepatitis C; SN = sensory neuropathy.
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Affiliation(s)
- C L Cherry
- The Alfred Hospital, Melbourne, Victoria 3004, Australia.
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Abstract
Cryoglobulins are serum immunoglobulins that precipitate at temperatures below 37 degrees C and re-dissolve on warming. Cryoglobulinaemia leads to variable symptoms including characteristic purpura, ischaemia of extremities, renal failure, peripheral neuropathy, abdominal pain secondary to intestinal ischaemia and arthralgias. Cryoglobulin testing is underutilized in clinical practice. It has been neglected in clinical laboratories and by clinicians due to several factors, such as the length of time it takes for serum cryoglobulin analysis to be performed in the laboratory, the perceived difficulty in getting optimal sampling conditions and a failure to appreciate that even apparently low levels of cryoglobulin can be associated with severe symptoms in some patients. The most important variable confounding standardization of cryoglobulin testing is improper sample handling. A recent report critically appraising the current practice of cryoglobulin evaluation in 137 laboratories in Europe by United Kingdom National External Quality Assurance Scheme (UKNEQAS) illustrated the wide variability in practice. Although many clinical laboratories perform cryoglobulin evaluation, there are widespread differences in the methodology used and the care with which this is carried out and this leads to considerable intralaboratory and interlaboratory variability. The most common sources of error are false-negative results due to loss of cryoprecipitate during transport and storage. Better standardization is needed to avoid missed diagnoses and improve the comparability of results. Laboratories should ensure that sample temperature is maintained at 37 degrees C until the serum is separated. In this article, we briefly review the classification and clinical features of cryoglobulins and suggest best practice guidelines for laboratory detection and identification of cryoglobulins.
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Affiliation(s)
- Ravishankar Sargur
- Clinical Immunology Unit, Department of Immunology, Northern General Hospital, Herries Road, Sheffield S5 8YD, UK.
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Osztovits J, Horváth T, Abonyi M, Tóth T, Visnyei Z, Bekö G, Csák T, Lakatos PL, Littvay L, Fehér J, Kempler P, Kollai M, Szalay F. Chronic hepatitis C virus infection associated with autonomic dysfunction. Liver Int 2009; 29:1473-1478. [PMID: 19602137 DOI: 10.1111/j.1478-3231.2009.02075.x] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/13/2023]
Abstract
BACKGROUND Impaired autonomic function has been described in patients with chronic liver diseases from different aetiologies, and has proven to be a poor prognostic indicator. To date, it is not known how chronic hepatitis C virus (HCV) infection affects the autonomic nervous system. AIMS In the present study, we compared cardiovagal autonomic function in patients with chronic HCV infection and healthy controls and examined the relation between autonomic function and serum levels of aminotransferases, HCV RNA, cryoglobulins, albumin and glucose. METHODS Autonomic function was assessed in 45 treatment-naïve patients with chronic HCV infection and in 40 healthy controls by determining spontaneous baroreflex sensitivity (BRS) and heart rate variability (HRV) indices. The R-R interval was determined by electrocardiogram recording; continuous radial artery pressure was monitored simultaneously by applanation tonometry. Laboratory analyses and quantitative polymerase chain reaction for serum HCV RNA level were performed by standard procedures. RESULTS BRS and HRV time and frequency domain indices were lower in patients with HCV infection compared with healthy controls [7.1+/-3.4 vs. 11.5+/-6.5 ms/mmHg for BRS, 168.5+/-160.9 vs. 370.7+/-349.4 ms(2) for low-frequency HRV (mean+/-SD); P<0.01]. Multivariate analysis showed that autonomic dysfunction in HCV-infected patients correlated with elevated alanine aminotransferase levels, but was not associated with serum HCV RNA levels and cryoglobulins. CONCLUSION Our results suggest that impaired autonomic function is caused by chronic HCV infection. Further studies are needed, however, to identify the underlying mechanisms.
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Affiliation(s)
- János Osztovits
- 1st Department of Internal Medicine, Semmelweis University, Budapest, Hungary.
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Ghoneimy ATE, Hasanien A, Ramzy GM, Youssof AM, Elsayed M, Shalaby NM, Hafez HA, Elfayomi N, Shalaby Z. Hepatitis C virus and peripheral neurological complications in Egyptian patients. Arab J Gastroenterol 2009. [DOI: 10.1016/j.ajg.2009.09.002] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
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Casato M, Carlesimo M, Francia A, Timarco C, Antenucci A, Bove M, Martini H, Visentini M, Fiorilli M, Conti L. Influence of inherited and acquired thrombophilic defects on the clinical manifestations of mixed cryoglobulinaemia. Rheumatology (Oxford) 2008; 47:1659-63. [DOI: 10.1093/rheumatology/ken303] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023] Open
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Johnson RT, Power C. Emerging issues in neurovirology: new viruses, diagnostic tools, and therapeutics. Neurol Clin 2008; 26:855-64, xi. [PMID: 18657730 PMCID: PMC7132743 DOI: 10.1016/j.ncl.2008.04.003] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
In the current era of escalating globalization with rapid transport, changing climate, and an ever growing human population with associated changes in lifestyle, poverty, and war, the emergence of new neurologic infections is accelerated. Understanding their origins using epidemiologic and molecular tools will contribute to improved control of agent spread throughout vulnerable populations. Although few interventions are effective in acute epidemics, the prompt identification of new infectious agents and the roll-out of vaccines together with new antiviral and neuroprotective drugs are promising for the management of future epidemics.
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Affiliation(s)
- Richard T Johnson
- Department of Neurology, The Johns Hopkins Hospital, Pathology 627, Baltimore, MD 21287, USA
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Bova C, Jaffarian C, Himlan P, Mangini L, Ogawa L. The Symptom Experience of HIV/HCV-Coinfected Adults. J Assoc Nurses AIDS Care 2008; 19:170-80. [PMID: 18457758 PMCID: PMC2405888 DOI: 10.1016/j.jana.2008.01.003] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2007] [Accepted: 01/14/2008] [Indexed: 02/06/2023]
Abstract
Hepatitis C virus (HCV) infection has emerged as a major problem for adults with HIV infection. This report describes the symptom experience of HIV/HCV-coinfected adults at entry into a longitudinal mixed-method study. In-depth qualitative interviews and a standardized quantitative symptom measure were used to capture the symptom experiences of 39 (46% women) HIV/HCV-coinfected patients. Four major themes emerged from the qualitative interviews: (a) difficulty differentiating between HIV and HCV-related symptoms, (b) commonly cited HCV-related symptoms, (c) ways to control or manage HCV-related symptoms, and (d) lack of symptoms or tests to monitor HCV disease. Participants reported an average of 10 different symptoms and a mean symptom experience score of 18.33 (range = 2-47). Results show the significant symptom burden experienced by HIV/HCV-coinfected adults. However, results suggest that the prevalence of symptoms for HIV/HCV-coinfected patients may not be greater than those experienced by patients with HIV infection alone.
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Affiliation(s)
- Carol Bova
- Associate Professor, University of Massachusetts Worcester, Graduate School of Nursing, 55 Lake Avenue North, Worcester, MA 01655, (508) 856-1848,
| | - Carol Jaffarian
- Instructor, University of Massachusetts Worcester, Graduate School of Nursing, 55 Lake Avenue North, Worcester, MA 01655, (508) 856-8655,
| | - Pauline Himlan
- Nurse Practitioner, UMass Memorial Health Care, 119 Belmont Street, Worcester, MA 01605, (508) 334-6127,
| | - Linda Mangini
- Nurse Practitioner, UMass Memorial Health Care, 55 Lake Avenue North Worcester, MA 01655, (508) 856-6027,
| | - Lisa Ogawa
- Research Assistant, University of Massachusetts Worcester, Graduate School of Nursing, 55 Lake Avenue North, Worcester, MA 01655, (508) 856-1848,
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Abstract
PURPOSE OF REVIEW Infectious neuropathy affects a large number of people worldwide. There is evidence of direct involvement of nerves by the infective agent, from the immune reaction of the patient or secondary to the toxicity of the drugs used during treatment. This group of neuropathies is often treatable or preventable. RECENT FINDINGS There is a complex clinical picture of the neuropathy of leprosy, different pathological features and immunological mechanisms. If the skin is unaffected in leprosy it is not always easy to demonstrate that the neuropathy is due to leprosy. Peripheral neuropathy in patients with chronic infection with hepatitis C virus may be due to the virus, the development of vasculitis or direct neurotoxic effects of the treatment. Peripheral neuropathy has become the chief neurological syndrome in individuals infected with HIV-1. The antiretroviral therapies themselves can cause peripheral neuropathies clinically indistinguishable from those caused by the virus. The occurrence of chronic polyneuropathy as a late manifestation in Lyme disease is extremely rare and is not well understood. SUMMARY Although infectious neuropathies are very frequent, mainly in developing countries, further studies are needed to elucidate their mechanisms of action, focusing on preventive interventions.
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Bibliography. Current world literature. Neuro-muscular diseases: nerve. Curr Opin Neurol 2007; 20:600-4. [PMID: 17885452 DOI: 10.1097/wco.0b013e3282efeb3b] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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Younis LK, Talaat FM, Deif AH, Borei MF, Reheim SMA, El Salmawy DH. Immunohistochemical detection of HCV in nerves and muscles of patients with HCV associated peripheral neuropathy and myositis. Int J Health Sci (Qassim) 2007; 1:195-202. [PMID: 21475428 PMCID: PMC3068633] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/30/2023] Open
Abstract
BACKGROUND Chronic hepatitis C Virus (HCV) infection may be associated with numerous extrahepatic manifestations, such as mixed cryoglobulinaemia, membranoproliferative glomerulonephritis, sicca syndrome. Cryoglobulinaemia (CG) is a condition characterized by the presence of serum proteins that reversibly precipitate in the cold. The objective of the present work was to study the histopathological changes in neuromuscular biopsies in patients with HCV associated peripheral neuropathy, or myopathy; with and without cryoglobulinemia, and to assess the presence of HCV in nerve and muscle tissues of those patients which might clarify some pathogenetic mechanisms for neuropathy, and myopathy associated with HCV. METHODS The study was conducted on 17 cases of HCV infected patients with peripheral neuropathy and myositis. All patients were subjected to thorough laboratory investigations, neurological examination, electrophysiologic studies including nerve conduction, and needle EMG studies. RESULTS Histopathological examination of nerve biopsies showed features of vascultis in 2/10 cases, interstitial inflammatory infiltrates in 5/10. Muscle biopsies showed intense inflammatory reaction, degenerative changes in the muscles of 3/10 cases diagnosed as myositis. Immunohistochemical results, showed in nerve biopsies, 7/10 cases with positive reaction for HCV with nuclear and perinuclear staining.. Two patients showed positive reaction in the epineural, and endoneural blood vessels and a negative reaction in nerve bundles, while in five patients, reaction was only positive in the nerve bundles. In muscle biopsies, 7/10 cases showed positive reaction for HCV in the nuclei of the muscle fibers, including the cases presented with myositis. CONCLUSION The presence of HCV particles in nerve and muscle biopsies of patients with peripheral neuropathy suggests a virus triggered immune mediated mechanism.
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Abstract
Cryoglobulinemia refers to the presence in serum of immunoglobulins that precipitate at a cold temperature. Type I cryoglobulins are single monoclonal immunoglobulins usually associated with haematological disorders. Types II and III are mixed cryoglobulins, composed of monoclonal or polyclonal IgM respectively, having rheumatoid factor activity that bind to polyclonal immunoglobulins. Mixed cryoglobulinemia (MC) syndrome is a consequence of immune-complex mediated vasculitis and is characterized by a typical clinical triad: purpura, weakness, arthralgias; many organs particularly kidney and peripheral nervous system may be involved. MC may be associated with infectious and systemic disorders and since 1990 studies have demonstrated that hepatitis C virus (HCV) may be considered the principal trigger of the disease. The relation between MC and HCV infection shows new insights in the interpretation of the link between viral infection, autoimmune phenomena and lymphoproliferative disorders evolution. In fact, the virus chronically stimulates B-cell polyclonal proliferation from which a monoclonal population may emerge. In symptomatic patients with HCV related MC therapeutic strategy should include an attempt at viral eradication. Antiviral therapy may also be effective in determining the regression of B-cell lymphoproliferative disorder. Rituximab could represent a safe and effective alternative to standard immunosuppression and exerts selective B-cell control.
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Affiliation(s)
- Alessandra Tedeschi
- Department Oncology/Haematology, Division of Haematology, Nigurda Ca' Granda Hospital Milano, Italy.
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