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Introduction: Peripheral neuropathy is common in clinical practice, with a reported prevalence of 2.4% in the general population. There are numerous aetiologies for peripheral neuropathy like diabetes, ischaemia, vasculitis, inflammatory demyelinating disorders, nutritional deficiencies, paraproteinemic disorders, paraneoplastic syndromes, toxic exposures, and hereditary neuropathies. An exhaustive haematological, biochemical, and serological work-up, cerebrospinal fluid evaluation, electrodiagnostic tests, and nerve biopsy are required when overlapping clinical features present a diagnostic challenge. Aim: To analyse the histopathological characteristics of nerve biopsies in individuals with peripheral neuropathy. Materials and methods: This cross-sectional study was conducted in the Department of Pathology at Kasturba Medical College from January 2011 to December 2016. Nerve biopsies received in the Department of Pathology, Kasturba Medical College and Hospitals in the Ambedkar Circle and Attavar area, as well as at Government Wenlock Hospital, Mangaluru, Karnataka, India were studied. Clinical and laboratory data were collected from biopsy requisition forms and patient case records from the aforementioned hospitals. Results were presented in numbers and percentages. Results: A total of 134 nerve biopsies were included in the study. The age range of all cases studied was 7-86 years, with a mean age of 51.8 years. The study population consisted of 63.4% males and 36.6% females, resulting in a male-to-female ratio of 1.7:1. Vasculitic Neuropathy (VN) accounted for 38.1% cases, followed by chronic inflammatory neuropathies (21.7%) and Diabetic Neuropathy (DN) (12.6%). Other diagnosis included ischaemic neuropathy (6.7%), Hereditary Motor and Sensory Neuropathy (HMSN) (3.7%), subacute inflammatory demyelinating neuropathy (3.0%), as well as two cases each of Hansen’s neuritis, amyloid neuropathy, and acute inflammatory demyelinating neuropathy (1.5% each). One case of toxic neuropathy (0.7%) was identified, while 9.0% of cases displayed histological features that were either non specific or not characteristic of any specific diagnosis. Conclusion: Vasculitic neuropathy was found to be the most common aetiology of peripheral neuropathy, followed by Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) and DN. The histopathological examination of nerve biopsies is a useful tool in distinguishing between diseases with overlapping clinical features, confirming or excluding vasculitis, and diagnosing hereditary conditions in settings where genetic testing is unavailable or unaffordable.

Introduction: Mononeuritis multiplex is frequently related to vasculitic neuropathy and has been reported only sporadically as an adverse event of immune checkpoint inhibitors. Methods: Case series of three patients with mononeuritis multiplex--all with mesothelioma--identified in the databases of two French clinical networks (French Reference Center for Paraneoplastic Neurological Syndromes, Lyon; OncoNeuroTox, Paris; January 2015--October 2022) set up to collect and investigate n-irAEs on a nationwide level. Results: Three patients (male; median age 86 years; range 72--88 years) had pleural mesothelioma and received 10, 4, and 6 cycles, respectively, of first-line nivolumab plus ipilimumab combined therapy. In patient 1, the neurological symptoms involved the median nerves, and in the other two patients, there was a more diffuse distribution; the symptoms were severe (common terminology criteria for adverse events, CTCAE grade 3) in all patients. Nerve conduction studies indicated mononeuritis multiplex in all patients. Peripheral nerve biopsy demonstrated necrotizing vasculitis in patients 1 and 3 and marked IgA deposition without inflammatory lesions in patient 2. Immune checkpoint inhibitors were permanently withdrawn, and corticosteroids were administered to all patients, leading to complete symptom regression (CTCAE grade 0, patient 2) or partial improvement (CTCAE grade 2, patients 1 and 3). During steroid tapering, patient 1 experienced symptom recurrence and spreading to other nerve territories (CTCAE grade 3); he improved 3 months after rituximab and cyclophosphamide administration. Discussion: We report the occurrence of mononeuritis multiplex, a very rare adverse event of immune checkpoint inhibitors, in the three patients with mesothelioma. Clinicians must be aware of this severe, yet treatable adverse event. [ABSTRACT FROM AUTHOR]

IntroductionMononeuritis multiplex is frequently related to vasculitic neuropathy and has been reported only sporadically as an adverse event of immune checkpoint inhibitors.MethodsCase series of three patients with mononeuritis multiplex—all with mesothelioma—identified in the databases of two French clinical networks (French Reference Center for Paraneoplastic Neurological Syndromes, Lyon; OncoNeuroTox, Paris; January 2015–October 2022) set up to collect and investigate n-irAEs on a nationwide level.ResultsThree patients (male; median age 86 years; range 72–88 years) had pleural mesothelioma and received 10, 4, and 6 cycles, respectively, of first-line nivolumab plus ipilimumab combined therapy. In patient 1, the neurological symptoms involved the median nerves, and in the other two patients, there was a more diffuse distribution; the symptoms were severe (common terminology criteria for adverse events, CTCAE grade 3) in all patients. Nerve conduction studies indicated mononeuritis multiplex in all patients. Peripheral nerve biopsy demonstrated necrotizing vasculitis in patients 1 and 3 and marked IgA deposition without inflammatory lesions in patient 2. Immune checkpoint inhibitors were permanently withdrawn, and corticosteroids were administered to all patients, leading to complete symptom regression (CTCAE grade 0, patient 2) or partial improvement (CTCAE grade 2, patients 1 and 3). During steroid tapering, patient 1 experienced symptom recurrence and spreading to other nerve territories (CTCAE grade 3); he improved 3 months after rituximab and cyclophosphamide administration.DiscussionWe report the occurrence of mononeuritis multiplex, a very rare adverse event of immune checkpoint inhibitors, in the three patients with mesothelioma. Clinicians must be aware of this severe, yet treatable adverse event.

Abstract Background Carpal tunnel syndrome is the most common focal mononeuropathy which presents with pain in the wrist and hand, paresthesia, loss of sensation in the distribution of the median nerve, and in more severe cases, weakness and atrophy of the thenar muscles. Meanwhile, carpal tunnel syndrome can present as an initial manifestation of underlying systemic vasculitis disorder and result in severe physical disabilities. Case presentation A 27-year-old Iranian man was referred to our electrodiagnosis center with a clinical diagnosis of carpal tunnel syndrome in April 2020. Surgical intervention had been taken into account for him because of unsuccessful conservative therapies. On admission, thenar eminence was reduced. Electrodiagnostic findings were not compatible with median nerve entrapment at the wrist. All sensory modalities in the distribution of the right median nerve were decreased. Additionally, a mild increase in erythrocyte sedimentation rate was noted in laboratory tests. Because of the high vasculitis suspicion, we recommended the nerve biopsy and/or starting a high-dose corticosteroid. However, the surgery release was performed. After 6 months, the patient was referred for progressive weakness and numbness in the upper and lower limbs. After documentation of vasculitis neuropathy by biopsy, a diagnosis of non-systemic vasculitic neuropathy was confirmed. A rehabilitation program started immediately. Rehabilitation led to gradual improvement and recovery of function and muscle strength, and no complications remained, except mild leg paralysis. Conclusions Physicians should be suspicious of the median nerve vasculitis mononeuropathy in a patient with carpal tunnel syndrome-like symptoms. Median nerve vasculitis mononeuropathy as an initial presenting feature of vasculitis neuropathy can further result in severe physical impairments and disabilities.

Abstract Background No controlled studies for non-systemic vasculitic neuropathy treatment exist (NSVN). We compared the treatment response to induction therapy commonly used in clinical practice in NSVN. Methods In this retrospective single-center study, 43 patients with biopsy-proven NSVN were analyzed. Patients were subdivided into groups depending on their initial treatment. Relapse rates, changes of motor and sensory symptoms, adverse events, predictors of relapses, and second-line treatment were compared. Results Initial treatment regimens were corticosteroid monotherapy, cyclophosphamide monotherapy, pulsed corticosteroid therapy, and combination therapy. Discontinuation due to adverse events occurred in 6 of 43 patients. Clinical data did not differ between treatment groups. Within 12 months, 24.3% of patients relapsed. The median time to relapse was 4 (1.5, 6) months. No relapse occurred in the combination therapy group. However, there was no statistically significant difference in relapse-free survival between treatment groups (p = 0.58). Neither clinical data nor biopsy analysis predicted relapses sufficiently. As a second-line treatment, cyclophosphamide as mono- or combination therapy was used (7 of 9 patients) most frequently. One patient was treated with methotrexate, and one with IVIG. Conclusions Induction therapy used in clinical practice is effective and mainly well-tolerated in NSVN. Our data do not support an overall advantage of cyclophosphamide over corticosteroid monotherapy. Controlled trials comparing the effectiveness of induction and maintenance therapy in NSVN are warranted.

Background: Carpal tunnel syndrome is the most common focal mononeuropathy which presents with pain in the wrist and hand, paresthesia, loss of sensation in the distribution of the median nerve, and in more severe cases, weakness and atrophy of the thenar muscles. Meanwhile, carpal tunnel syndrome can present as an initial manifestation of underlying systemic vasculitis disorder and result in severe physical disabilities. Case presentation: A 27-year-old Iranian man was referred to our electrodiagnosis center with a clinical diagnosis of carpal tunnel syndrome in April 2020. Surgical intervention had been taken into account for him because of unsuccessful conservative therapies. On admission, thenar eminence was reduced. Electrodiagnostic findings were not compatible with median nerve entrapment at the wrist. All sensory modalities in the distribution of the right median nerve were decreased. Additionally, a mild increase in erythrocyte sedimentation rate was noted in laboratory tests. Because of the high vasculitis suspicion, we recommended the nerve biopsy and/or starting a high-dose corticosteroid. However, the surgery release was performed. After 6 months, the patient was referred for progressive weakness and numbness in the upper and lower limbs. After documentation of vasculitis neuropathy by biopsy, a diagnosis of non-systemic vasculitic neuropathy was confirmed. A rehabilitation program started immediately. Rehabilitation led to gradual improvement and recovery of function and muscle strength, and no complications remained, except mild leg paralysis. Conclusions: Physicians should be suspicious of the median nerve vasculitis mononeuropathy in a patient with carpal tunnel syndrome-like symptoms. Median nerve vasculitis mononeuropathy as an initial presenting feature of vasculitis neuropathy can further result in severe physical impairments and disabilities. [ABSTRACT FROM AUTHOR]

Vasculitic neuropathy can present associated with both primary and secondary systemic vasculitis as a result from underlying diseases such as rheumatic diseases and infections, Moreover, confined vasculitis in the peripheral nervous system may be present. Thus, the diagnosis and management of vasculitic neuropathy require multidisciplinary approaches. Current views as well as relevant clinical research on the diagnosis, assessment, and management of vasculitic neuropathy are reviewed to suggest appropriate treatment strategies. We searched PubMed and Google Scholar for reports published between July 2017 and July 2022. For the treatment of vasculitic neuropathy, determining the causative primary disease is important and often requires diagnosis by tissue biopsy. Due to the scarce research on the treatment of vasculitic neuropathy, treatment is empirically based on findings from studies of systemic vasculitides involving other organs, particularly antineutrophil cytoplasmic antibody-associated vasculitis. In addition to conventional glucocorticoids and immunosuppressive agents, complement-targeted therapy, anti-B-cell therapy, and disease-specific molecular targeted therapies have recently gained relevance. Future research is needed to develop new patient-specific therapeutic options. [ABSTRACT FROM AUTHOR]

Abstract Background Eosinophilic granulomatosis with polyangiitis (EGPA) is associated with vasculitic neuropathy and being rare can present as subacute symmetric sensorimotor quadriparesis mimicking Guillain–Barre syndrome (GBS). It warrants timely diagnosis as treatment for both conditions is different and vasculitic neuropathy needs long-term immunosuppression. Nerve biopsy of our patient showed eosinophilic infiltration along with mononuclear infiltrate. Typical histopathological presentations of EGPA are different among different organs and eosinophilic infiltration is rarely observed in peripheral nerve and kidney involvements. Case presentation A 49-year-old female with a history of asthma with 3-week duration of acute onset ascending weakness, preceded by severe pain and burning in glove and stocking pattern. Nerve conduction studies could not rule out Guillain–Barre syndrome initially, but subsequent studies show axonal affection and she received intravenous immunoglobulin (IVIg) but her weakness progressed after slight improvement. Her bloodwork revealed marked eosinophilia (> 50%) with computed tomography (CT) paranasal sinuses showing pansinusitis with background history of asthma led us towards eosinophilic granulomatosis with polyangiitis and later antineutrophil cytoplasmic antibodies came out positive with nerve biopsy showing perivascular mononuclear inflammation with eosinophils. She was started on steroids immediately and then received intravenous rituximab in view of long-term immunosuppression with maintenance steroids and on follow-up she improved. Conclusion Eosinophilic granulomatosis with polyangiitis is a small-vessel vasculitis associated with antineutrophil cytoplasmic antibodies with significant paranasal sinuses involvement. Mononeuritis multiplex is the most common presentation of vasculitic neuropathy of eosinophilic granulomatosis with polyangiitis, but they can mimic Guillain–Barre syndrome and should always be considered in the differential diagnosis, since the treatment strategies for these conditions are radically different.

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis is a systemic disorder that frequently affects the peripheral nervous system and consists of three distinct conditions: microscopic polyangiitis (MPA), granulomatosis with polyangiitis (GPA, previously Wegener's granulomatosis), and eosinophilic granulomatosis with polyangiitis (EGPA, previously Churg-Strauss syndrome). The neuropathic features associated with this condition usually include mononeuritis multiplex, which reflects the locality of lesions. Findings suggestive of vasculitis are usually found in the epineurium and occur diffusely throughout the nerve trunk. Nerve fiber degeneration resulting from ischemia is sometimes focal or asymmetric and tends to become conspicuous at the middle portion of the nerve trunk. The attachment of neutrophils to endothelial cells in the epineurial vessels is frequently observed in patients with ANCA-associated vasculitis; neutrophils play an important role in vascular inflammation by binding of ANCA. The positivity rate of ANCA in EGPA is lower than that in MPA and GPA, and intravascular and tissue eosinophils appear to participate in neuropathy. Immunotherapy for ANCA-associated vasculitis involves the induction and maintenance of remission to prevent the relapse of the disease. A combination of glucocorticoids along with cyclophosphamide, rituximab, methotrexate, or mycophenolate mofetil is considered depending on the severity of the condition of the organ to induce remission. A combination of low-dose glucocorticoids and azathioprine, rituximab, methotrexate, or mycophenolate mofetil is recommended to maintain remission. The efficacy of anti-interleukin-5 therapy (i.e., mepolizumab) was demonstrated in the case of refractory or relapsing EGPA. Several other new agents, including avacopan, vilobelimab, and abatacept, are under development for the treatment of ANCA-associated vasculitis. Multidisciplinary approaches are required for the diagnosis and management of the disorder because of its systemic nature. Furthermore, active participation of neurologists is required because the associated neuropathic symptoms can significantly disrupt the day-to-day functioning and quality of life of patients with ANCA-associated vasculitis. [ABSTRACT FROM AUTHOR]

Background: Eosinophilic granulomatosis with polyangiitis (EGPA) is associated with vasculitic neuropathy and being rare can present as subacute symmetric sensorimotor quadriparesis mimicking Guillain-Barre syndrome (GBS). It warrants timely diagnosis as treatment for both conditions is different and vasculitic neuropathy needs long-term immunosuppression. Nerve biopsy of our patient showed eosinophilic infiltration along with mononuclear infiltrate. Typical histopathological presentations of EGPA are different among different organs and eosinophilic infiltration is rarely observed in peripheral nerve and kidney involvements. Case presentation: A 49-year-old female with a history of asthma with 3-week duration of acute onset ascending weakness, preceded by severe pain and burning in glove and stocking pattern. Nerve conduction studies could not rule out Guillain-Barre syndrome initially, but subsequent studies show axonal affection and she received intravenous immunoglobulin (IVIg) but her weakness progressed after slight improvement. Her bloodwork revealed marked eosinophilia (> 50%) with computed tomography (CT) paranasal sinuses showing pansinusitis with background history of asthma led us towards eosinophilic granulomatosis with polyangiitis and later antineutrophil cytoplasmic antibodies came out positive with nerve biopsy showing perivascular mononuclear inflammation with eosinophils. She was started on steroids immediately and then received intravenous rituximab in view of long-term immunosuppression with maintenance steroids and on follow-up she improved. Conclusion: Eosinophilic granulomatosis with polyangiitis is a small-vessel vasculitis associated with antineutrophil cytoplasmic antibodies with significant paranasal sinuses involvement. Mononeuritis multiplex is the most common presentation of vasculitic neuropathy of eosinophilic granulomatosis with polyangiitis, but they can mimic Guillain-Barre syndrome and should always be considered in the differential diagnosis, since the treatment strategies for these conditions are radically different. [ABSTRACT FROM AUTHOR]

Background: Vasculitic neuropathies are an uncommon heterogeneous group of nerve disorders characterized by inflammation of the vasa nervorum, which may be either systemic vasculitic neuropathy (SVN) or non-SVN (NSVN). Settings and Design: This is a retrospective, observational study. Materials and Methods: Nerve biopsy-proven cases of vasculitic neuropathy (VN) from January 2011 to December 2017 were included in the study. Results: Twenty-five percent (40/156) patients had vasculitis on biopsy, 62.5% were male and the mean age was 52.8 ± 14.9 years. The median (interquartile range) duration of symptoms before diagnosis was 75 (345) days. Thirty (75%) patients had NSVN and 10 (25%) patients had SVN. The clinical pattern of peripheral nervous system involvement was as follows: 20 (50%) had polyneuropathy, 13 (32.5%) had mononeuritis multiplex, and 7 (32.5%) had polyradiculoneuropathy. Twenty-three (57.5%) patients received immunomodulatory therapy. Conclusion: VN has a wide spectrum of clinical presentation. High index of suspicion followed by nerve biopsy is needed for diagnosis. Early treatment may improve prognosis in this group of patients.

Vasculitis is a clinically diverse group of diseases with histopathological signs of blood vessel inflammation, which contributes to vascular damage and ischemic damage to the affected tissues. Vasculitic neuropathy is a common complication of the primary systemic vasculitides, such as polyartertis nodosa and antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis, systemic diseases of the connective tissue - systemic lupus erythematosus and Sjogren syndrome, vasculitis associated with infection, most often viral hepatitis C and B and non - systemic vasculitis neuropathy. Vessels of medium and small caliber are involved in the pathological process in these diseases. With all vasculitis, except for those caused by the direct effect of the infectious trigger on the blood vessel walls, the main pathogenetic mechanism is an autoimmune process with the development of vasa nervorum vasculitis - small arteries and vessels that supply peripheral nerves, and the outcome - nerve ischemia. The classic clinical presentation is an acute or subacute painful multifocal neuropathy that has a predilection for the lower extremities, affects two or more named nerves, and progresses in a step wise manner. However, vasculitic neuropathy can manifest in a variety of ways, including asymmetric polyneuropathies and distal symmetric sensory neuropathies, and it also can be slowly progressive, particularly in cases of nonsystemic vasculitic neuropathy (NSVN), a form of vasculitis that clinically remains restricted to peripheral nerves. Nerve biopsy can help establish the diagnosis of a systemic vasculitis, particularly when other organ involvement is not clinically apparent, and is required for diagnosis of NSVN. Neuropathy due to systemic vasculitis should be treated in accordance with the recommendations for the treatment of the underlying disease. In NSVH, the main medicine of choice are glucocrticoids, and in severe/progressive cases, pulse therapy with cyclophosphamide.

Objective Limited evidence exists to guide treatment of refractory vasculitic neuropathy. While rituximab (RTX) and IVIG have both been proposed as individual treatment options for these patients, combination therapy has never been reported. Methods Written informed consent was obtained from three patients with refractory vasculitic neuropathy who were treated with combination RTX and IVIG. Their electronic medical records were reviewed and clinical and functional outcomes were reported. Results Two male patients with non-systemic vasculitic neuropathy and one male patient with granulomatosis with polyangiitis were treated with combination RTX and IVIG therapy. All three patients demonstrated clinical improvement with at least partial functional recovery and a reduction in corticosteroid dose. This combination was generally well tolerated. Conclusions Combination RTX and IVIG therapy may be a safe and effective treatment option for patients with refractory vasculitic neuropathy. Further studies are needed to better characterize the risks and benefits of this combination. [ABSTRACT FROM AUTHOR]

Immune axonal neuropathies are a particular group of immune-mediated neuropathies that occasionally accompany systemic autoimmune rheumatic diseases such as connective tissue dissorders and primary systemic vasculitides. Apart from vasculitis of vasa nervorum, various other mechanisms are involved in their pathogenesis, with possible therapeutic implications. Immune axonal neuropathies have highly heterogeneous clinical presentation and course, ranging from mild chronic distal sensorimotor polyneuropathy to severe subacute mononeuritis multiplex with rapid progression and constitutional symptoms such as fever, malaise, weight loss and night sweats, underpinning a vasculitic process. Sensory neuronopathy (ganglionopathy), small fiber neuropathy (sensory and/or autonomic), axonal variants of Guillain-Barré syndrome and cranial neuropathies have also been reported. In contrast to demyelinating neuropathies, immune axonal neuropathies show absent or reduced nerve amplitudes with normal latencies and conduction velocities on nerve conduction studies. Diagnosis and initiation of treatment are often delayed, leading to accumulating disability. Considering the lack of validated diagnostic criteria and evidence-based treatment protocols for immune axonal neuropathies, this review offers a comprehensive perspective on etiopathogenesis, clinical and paraclinical findings as well as therapy guidance for assisting the clinician in approaching these patients. High quality clinical research is required in order to provide indications and follow up rules for treatment in immune axonal neuropathies related to systemic autoimmune rheumatic diseases.

Background: Perls Prussian blue stain (PPB) for hemosiderin, a marker of vascular injury is often employed as an adjunct in the diagnosis of vasculitic neuropathies. However, inflammation/vascular injury is also seen in leprosy, immune mediated, paraproteinemic, diabetic neuropathies, etc. The frequency of detection of hemosiderin in these neuropathies and its utility in diagnosis of vasculitis has not been explored.Objective: We evaluated 208 peripheral nerve biopsies for hemosiderin deposits by PPB stain in vasculitis (78) and compared with inflammatory/immune neuropathies [leprous neuritis-32, chronic inflammatory demyelinating polyneuropathy (CIDP)-15, paraproteinemic neuropathies (POEMS)-12, diabetic neuropathy-37] and nonimmune neuropathies [Charcot-Marie-Tooth (CMT) disease-15, vitamin B12 deficiency-7, and ischemic neuropathy in aged-12)].Results: Hemosiderin deposits were most frequent in vasculitis (48.72%) [59.2% in systemic; 43.1% in nonsystemic vasculitides] and enhanced the sensitivity of diagnosis in "probable" vasculitis (34.48%) that lacked transmural inflammation. Hemosiderin was also detected in infectious/immune-mediated neuropathies (leprous neuritis-56%, POEMS-33.3%, diabetes-18.9%) but absent in CMT, B12 deficiency, and ischemic neuropathy. Hemosiderin deposits involved epineurium in vasculitis, compared to endoneurial/perineurial location in leprosy and perineurial in POEMS and diabetic neuropathy. The sensitivity of detection was high in vasculitic neuropathy (49.35%) compared to other inflammatory neuropathies (22.3%) (P < 0.05) with high specificity (77.69% [positive predictive value (PPV)-56.71%; negative predictive value (NPV)-71.6%]. The specificity increased to 89% if leprous neuropathy was excluded, with PPV-77.5% while NPV dropped to 68.5%.Conclusion: These findings suggest that PPB stain for detection of hemosiderin is a useful adjunct in diagnosis of vasculitic neuropathy with high specificity but low sensitivity. [ABSTRACT FROM AUTHOR]

Nerve biopsy represents the conclusive step in the diagnostic work-up of peripheral neuropathies, and its diagnostic yield is still debated. The aim of this study is to consider the impact of nerve biopsy on reaching a useful diagnosis in different peripheral neuropathies and its changing over time. We retrospectively analyzed 1,179 sural nerve biopsies performed in the period 1981–2017 at Neurological Clinic of Policlinico San Martino (Genoa). We relied on medical records and collected both clinical and pathological data in a database. Biopsy provided univocal diagnoses in 53% of cases (with an increase over time), multiple diagnostic options in 14%, while diagnosis was undetermined in 33% (undetermined reports decreased during the years). In 57% of patients, the pre-biopsy suspicion was confirmed, while in 43% sural biopsy modified the clinical diagnosis. The highest yield was in axonal neuropathies (29% undetermined reports vs. 40% in demyelinating and 48% in mixed neuropathies). In 68% of patients with vasculitic neuropathy, this etiology was already suspected, whereas in 32% nerve biopsy modified the clinical diagnosis. During the years, the number of annually performed biopsies decreased significantly (p = 0.007), with an increase in the mean age of patients (p < 0.0001). The percentage of hereditary neuropathies had a significant decrease (p = 0.016), while the rate of vasculitic and chronic inflammatory neuropathies increased (p < 0.0001). This is the largest Italian study addressing the yield of sural nerve biopsy. During the years, we observed a progressive refinement of the indication of this procedure, which confirms its utility for interstitial neuropathies, particularly if non-systemic vasculitic neuropathy is suspected.

Rheumatoid vasculitis which affects small-to-medium-sized vessels is a rare and late complication of rheumatoid arthritis. It is defined histologically as immune complex deposition in venules, capillaries and arterioles.1 Vasculitis in the vasa nervorum leads to infarction of peripheral nerves which leads to neuropathy. We present a case of mononeuritis multiplex due to rheumatoid vasculitis.

Peripheral neuropathy is a common feature of systemic vasculitis and can also occur when vessel wall inflammation is confined to the vasa nervorum, as a tissue-specific condition—non-systemic vasculitic neuropathy (NSVN). Typically, the clinical picture in both systemic and non-systemic cases is of a lower limb predominant, distal, asymmetric or multifocal neuropathy, which is painful and subacute in onset. For NSVN, nerve biopsy is required to make the diagnosis, and nerve biopsy also has a role when vasculitic neuropathy is suspected and a systemic process has not yet declared itself. Early recognition of the disorder is important, because it is treatable, and without treatment potentially disabling, or even lethal if part of an undiagnosed systemic process. Treatment is generally with combination therapy (glucocorticoid plus other immunosuppressant), after which motor and sensory recovery are likely to occur, albeit slowly, but the patient may be left with chronic neuropathic pain. [ABSTRACT FROM AUTHOR]

Nerve biopsy represents the conclusive step in the diagnostic work-up of peripheral neuropathies, and its diagnostic yield is still debated. The aim of this study is to consider the impact of nerve biopsy on reaching a useful diagnosis in different peripheral neuropathies and its changing over time. We retrospectively analyzed 1,179 sural nerve biopsies performed in the period 1981–2017 at Neurological Clinic of Policlinico San Martino (Genoa). We relied on medical records and collected both clinical and pathological data in a database. Biopsy provided univocal diagnoses in 53% of cases (with an increase over time), multiple diagnostic options in 14%, while diagnosis was undetermined in 33% (undetermined reports decreased during the years). In 57% of patients, the pre-biopsy suspicion was confirmed, while in 43% sural biopsy modified the clinical diagnosis. The highest yield was in axonal neuropathies (29% undetermined reports vs. 40% in demyelinating and 48% in mixed neuropathies). In 68% of patients with vasculitic neuropathy, this etiology was already suspected, whereas in 32% nerve biopsy modified the clinical diagnosis. During the years, the number of annually performed biopsies decreased significantly (p = 0.007), with an increase in the mean age of patients (p < 0.0001). The percentage of hereditary neuropathies had a significant decrease (p = 0.016), while the rate of vasculitic and chronic inflammatory neuropathies increased (p < 0.0001). This is the largest Italian study addressing the yield of sural nerve biopsy. During the years, we observed a progressive refinement of the indication of this procedure, which confirms its utility for interstitial neuropathies, particularly if non-systemic vasculitic neuropathy is suspected. [ABSTRACT FROM AUTHOR]

A 21-year-old female born of nonconsanguineous marriage presented with gradually progressive quadriplegia for 3 years. Weakness was distal more than proximal, with wasting. She also had moderate pain in extremities. She had significant weight loss. Clinically, she had lower motor neuron flaccid quadriplegia with absent deep tendon jerks. Sensations of touch and pain were diminished in bilateral feet till ankle joints. Peripheral nerves were not thickened. Nerve conduction study was suggestive of pure axonal sensorimotor polyneuropathy. All routine hematological and biochemical parameters, erythrocyte sedimentation rate, antinuclear antibodies, and antinuclear cytoplasmic antibodies were negative. Cerebrospinal fluid showed no cells, normal sugar, and raised proteins. Biopsy of sural nerve was suggestive of vasculitic neuropathy. This was a case of nonsystemic vasculitic neuropathy that responded to steroids.

Revisar la eficacia y seguridad del rituximab en neuropatía vasculítica (NV). Se realizó una búsqueda en la literatura de Medline y Embase hasta 2017. Los términos incluidos guardaron relación con «vasculitis», «neuropatía vasculítica» y «rituximab». Dicha búsqueda fue realizada por 2 revisores. El resultado principal fue la eficacia del rituximab. Tras seleccionar inicialmente 702 artículos, 5 de ellos permanecieron con un nivel de evidencia de entre 1+ y 3, y un grado de recomendación variable. En el único ensayo clínico incluido, el rituximab fue superior a la terapia convencional para vasculitis crioglobulinémica, mostrando NV un incremento en la tasa de retención farmacológica (64,3 vs. 3,5%; p < 0,001) y una menor tasa de efectos adversos graves (0,12 vs. 0,48). Los estudios de cohortes de pacientes con vasculitis crioglobulinémica incluyeron una mejora probada y una remisión completa/parcial de NV. En una serie de 5 casos de EGPA refractaria con NV, el 60% y el 20% de los pacientes lograron una remisión completa y parcial, respectivamente. Rituximab parece ser un tratamiento eficaz y seguro para NV, en el contexto de vasculitis crioglobulinémica. Se carece de evidencia sobre la eficacia específica de NV en el contexto de otras vasculitis. To review the efficacy and safety of rituximab in vasculitic neuropathy (VN) A literature search was performed on Medline and Embase up until 2017. It included terms related to "vasculitis","vasculitic neuropathy" and "Rituximab". Research was carried out by two reviewers. The main outcome was rituximab efficacy. Of an initial selection of 702 articles, 5 remained with a level of evidence between 1+ and 3 and variable recommendation degree. In the only clinical trial included, rituximab was superior to conventional therapy for cryoglobulinemic vasculitis with VN showing an increase in drug retention rate (64.3% vs. 3.5%; P <.001)and with a lower rate of serious adverse effects (.12 vs..48). Cohort studies of patients with cryoglobulinemic vasculitis showed improvement and complete/partial remission of VN. In a series of 5 cases of refractory EGPA suffering from VN, 60% and 20% of patients achieved complete and partial remission respectively. Rituximab seems an effective and safe treatment for VN in the context of cryoglobulinemic vasculitis. Evidence for specific efficacy in VN in the context of other types of vasculitis is lacking [ABSTRACT FROM AUTHOR]

Objective: To describe clinical, electrophysiological, and histopathological profile of vasculitic neuropathy in elderly subjects aged 65 years or more. Design: Retrospective chart review. Setting: Departments of Neurology and Neuropathology, National Institute of Mental Health and Neurosciences, Bengaluru, Karnataka, India. Patients and Methods: Elderly subjects, diagnosed vasculitic neuropathy by nerve biopsy over one decade, were studied. Results: The cohort consisted of 46 subjects. Symptom duration was 21.54 ± 33.53 months. Onset was chronic in majority (82.6%). Key features included paresthesias (89%), weakness (80%), sensory loss (70%), wasting (63%), and relapsing-remitting course (6.5%). Most Common clinico-electrophysiological patterns were distal symmetrical sensorimotor polyneuropathy - 19, mononeuritis multiplex - 9, and asymmetric sensorimotor neuropathy - 10. Diagnosis of vasculitis was not suspected before biopsy in 31 (67.3%). Nerve biopsy revealed definite vasculitis - 12, probable - 10, and possible - 24. Treatment included immunomodulatory agents (41), symptomatic medications only (9), and antiretroviral therapy (1). Twenty-four patients were followed up for mean period of 6.5 months. Outcome at last follow-up was improved (13), unchanged (8), and worsened (3). Conclusion: Vasculitis is an important, treatable cause of neuropathy in elderly. Nerve biopsy should be used judiciously for early diagnosis and appropriate treatment.

Rheumatoid vasculitis which affects small-to-medium-sized vessels is a rare and late complication of rheumatoid arthritis. It is defined histologically as immune complex deposition in venules, capillaries and arterioles.1 Vasculitis in the vasa nervorum leads to infarction of peripheral nerves which leads to neuropathy. We present a case of mononeuritis multiplex due to rheumatoid vasculitis. [ABSTRACT FROM AUTHOR]

Proteinase 3 anti-neutrophil cytoplasmic antibody (PR3-ANCA) is reported to be highly specific to vasculitis compared to myeloperoxidase (MPO)-ANCA. We report a case of a 19-year-old woman with chronic inflammatory demyelinating polyneuropathy (CIDP) with high PR3-ANCA positivity. The patient responded well to intravenous immunoglobulin plus oral steroid, and showed no signs of systemic vasculitis during the subsequent 10 months of follow-up. Our present case suggests that CIDP may accompany high PR3-ANCA levels, which should be differentiated from axonal neuropathy due to vasculitis.

Objective: To describe clinical, electrophysiological, and histopathological profile of vasculitic neuropathy in elderly subjects aged 65 years or more. Design: Retrospective chart review. Setting: Departments of Neurology and Neuropathology, National Institute of Mental Health and Neurosciences, Bengaluru, Karnataka, India. Patients and Methods: Elderly subjects, diagnosed vasculitic neuropathy by nerve biopsy over one decade, were studied. Results: The cohort consisted of 46 subjects. Symptom duration was 21.54 ± 33.53 months. Onset was chronic in majority (82.6%). Key features included paresthesias (89%), weakness (80%), sensory loss (70%), wasting (63%), and relapsing-remitting course (6.5%). Most Common clinico-electrophysiological patterns were distal symmetrical sensorimotor polyneuropathy - 19, mononeuritis multiplex - 9, and asymmetric sensorimotor neuropathy - 10. Diagnosis of vasculitis was not suspected before biopsy in 31 (67.3%). Nerve biopsy revealed definite vasculitis - 12, probable - 10, and possible - 24. Treatment included immunomodulatory agents (41), symptomatic medications only (9), and antiretroviral therapy (1). Twenty-four patients were followed up for mean period of 6.5 months. Outcome at last follow-up was improved (13), unchanged (8), and worsened (3). Conclusion: Vasculitis is an important, treatable cause of neuropathy in elderly. Nerve biopsy should be used judiciously for early diagnosis and appropriate treatment. [ABSTRACT FROM AUTHOR]

Introduction: The receptor for advanced glycation end products (RAGE) is a pattern recognition receptor expressed in tissues and cells, which plays a role in immunity. The activation of RAGE results in the translocation of nuclear factor kappa B (NF-κB) to the nucleus for expression of proinflammatory molecules. The role of the RAGE pathway in the pathogenesis of diabetic complications is well determined. We aimed to investigate the role of the RAGE pathway in axonal and vasculitic neuropathy. Methods: We immunoreacted nerve biopsy samples from 17 axonal neuropathy (AN), 11 vasculitic neuropathy (VN) and 12 hereditary neuropathy (as a control group) with liability to pressure palsy (HNPP) patients with antibodies to NF-κB and RAGE. Subsequently, we performed double staining with the antibodies to NF-κB or RAGE and T cells, macrophages and Schwann cells. Results: RAGE and NF-κB immunoreactivities were higher in the perivascular cuff and in endoneurial cells in VN than in AN and HNPP. Although there is no significant difference, nerve biopsies with AN showed higher NFκB and RAGE immunoreactivities than HNPP. The colocalization study showed that most of the NFκB- and RAGE-positive cells were CD8 (+) T cells in VN. In AN, all NFκB- and RAGE-positive cells were macrophages, whereas all NFκB- and RAGE-positive cells were Schwann cells in HNPP. Conclusion: The activation of the RAGE pathway predominant in CD8 (+) T cells underscores its role in VN. In AN patients, the immunoreactivity to NFκB and RAGE in macrophages may support their role in axonal degeneration without inflammatory milieu. [ABSTRACT FROM AUTHOR]

Vasculitis can affect the peripheral nervous system alone (nonsystemic vasculitic neuropathy) or can be a part of primary or secondary systemic vasculitis. In cases of pre-existing systemic vasculitis, the diagnosis can easily be made, whereas suspected vasculitic neuropathy as initial or only manifestation of vasculitis requires careful clinical, neurophysiological, laboratory and histopathological workout. The typical clinical syndrome is mononeuropathia multiplex or asymmetric neuropathy, but distal-symmetric neuropathy can frequently be seen. Standard treatments include steroids, azathioprine, methotrexate and cyclophosphamide. More recently the B-cell antibody rituximab and intravenous immunoglobulins have shown to be effective in some vasculitic neuropathy types. [ABSTRACT FROM PUBLISHER]

A 21-year-old female born of nonconsanguineous marriage presented with gradually progressive quadriplegia for 3 years. Weakness was distal more than proximal, with wasting. She also had moderate pain in extremities. She had significant weight loss. Clinically, she had lower motor neuron flaccid quadriplegia with absent deep tendon jerks. Sensations of touch and pain were diminished in bilateral feet till ankle joints. Peripheral nerves were not thickened. Nerve conduction study was suggestive of pure axonal sensorimotor polyneuropathy. All routine hematological and biochemical parameters, erythrocyte sedimentation rate, antinuclear antibodies, and antinuclear cytoplasmic antibodies were negative. Cerebrospinal fluid showed no cells, normal sugar, and raised proteins. Biopsy of sural nerve was suggestive of vasculitic neuropathy. This was a case of nonsystemic vasculitic neuropathy that responded to steroids. [ABSTRACT FROM AUTHOR]

Background: The differential diagnosis of chronic progressive multifocal asymmetric neuropathies is challenging. Vasculitic neuropathies, multifocal forms of chronic inflammatory demyelinating polyneuropathy, multifocal motor neuropathies, and asymmetric lower motor neuron disorders are important considerations. Case presentation: We report a patient with an unusually long 12-year course of nonsystemic vasculitic neuropathy prior to the development of systemic manifestations. Conclusion: We discuss some of the difficulties involved in the diagnosis of chronic progressive multifocal asymmetric neuropathies. [ABSTRACT FROM AUTHOR]

Introduction: Early comprehensive geriatric assessment (CGA) with good history-taking is essential in assessing the older adult. Case presentation: Our patient, a 75-year-old Caucasian woman, was originally admitted to hospital for investigation of iron deficiency anemia. During admission, she developed pneumonia and new intermittent atrial fibrillation in association with a right-sided weakness, which was felt to be new at the time. Following this episode, she was treated for a further chest infection and, despite clinical improvement, her inflammatory markers failed to settle satisfactorily. She was transferred to her local hospital for a period of rehabilitation where further neurological findings made the diagnosis of solely stroke questionable; these findings prompted further history-taking, investigations and input from other disciplines, thereby helping to arrive at a working diagnosis of vasculitic neuropathy. Conclusions: The case aims to highlight the importance of taking a good history and performing an early comprehensive assessment in the older adult. [ABSTRACT FROM AUTHOR]