Subacute Neuropathy Research Articles

Clinicopathologic Findings in Patients With Paraneoplastic Neuropathies and Antibodies Strongly Associated With Cancer.

Pathologic descriptions of peripheral nerve involvement in paraneoplastic neuropathies are sparse, mostly from autopsies focusing on CNS and dorsal root ganglia tissues. Here, we describe the clinicopathologic features of peripheral nerve biopsies in patients with paraneoplastic neurologic syndromes to expand the currently limited knowledge. Retrospective review of the Mayo Clinic electronic medical record from 1995 to 2022 for patients identified to have subacute onset neuropathy with paraneoplastic antibodies identified in our neuroimmunology laboratory having available nerve biopsies performed at the time of diagnosis. Patients with another cause of neuropathy not linked to their subacute onset were excluded. Nineteen patients met inclusion criteria: 4 with amphiphysin antibodies, 6 with antineuronal nuclear antibody (ANNA)-1 only, 3 with both ANNA-1 and collapsin response-mediator protein 5 (CRMP-5), 2 with ANNA-2, and 4 with CRMP-5 antibodies only. Fifteen biopsies had reduced the density of myelinated nerve fibers-4 with multifocality. Subperineurial edema was present in 17 biopsies. Prominent epineurial perivascular inflammation was present in 3 biopsies, all belonging to patients with a lumbosacral radiculoplexus neuropathy (LRPN) phenotype. Axonal loss, subperineurial edema, and an absence of prominent inflammation are the most common findings in nerve biopsies of patients with paraneoplastic antibodies strongly associated with cancer. The LRPN phenotype was the only subset with inflammatory collections. Paraneoplastic autoantibody testing should be considered in patients with subacute onset neuropathies, with or without interstitial inflammatory findings.

TS-HDS autoantibody: clinical characterization and utility from real-world tertiary care center experience.

To evaluate clinical utility of trisulfated-heparin disaccharide (TS-HDS) IgM testing from real-world tertiary care center experience. Medical records of patients with positive TS-HDS antibodies who were evaluated at Mayo Clinic from 2009 to 2022 were reviewed. Seventy-seven patients (50 females) had positive TS-HDS antibody. Median age was 48 (9-77) years. Median titer was 25,000 (range 11,000-350,000). Twenty-six patients (34%) did not have objective evidence of peripheral neuropathy. Nine patients (12%) had other known causes of neuropathy. Among the remaining 42 patients, half presented with subacute progressive course; the other half had chronic indolent course. Most common phenotypes were length-dependent peripheral neuropathy (n = 20, 48%), length-dependent small-fiber neuropathy (n = 11, 26%), and non-length-dependent small-fiber neuropathy (n = 7, 17%). Nerve biopsies showed epineurial inflammatory cell collections in 2 but no interstitial abnormalities in the remaining 7. The majority of intraepidermal nerve fiber densities (7/10), thermoregulatory sweat tests (12/21) and autonomic reflex screens (27/49) were normal. Post-immunotherapy improvement in mRS/INCAT disability score/pain was only seen in 13/42 (31%) TS-HDS IgM positive patients. Patients presenting with sensory ganglionopathy, non-length dependent small-fiber neuropathy, or subacute progressive neuropathy with and without TS-HDS antibody responded similarly to immunotherapy (40% vs 80%, p = 0.30). TS-HDS IgM has limited phenotypic or disease specificity; it was found to be positive among patients with various neuropathy phenotypes as well as patients without objective evidence of neuropathy. Clinical improvement with immunotherapy, although was observed in a small proportion of TS-HDS IgM seropositive patients, was not more frequent when compared to seronegative patients with similar presentations.

Nitrous oxide‐induced neurological disorders: an increasing public health concern

Neurological presentations resulting from nitrous oxide (N2 O) abuse are increasing in Australia and worldwide. Despite known neuropsychiatric sequelae, N2 O canisters remain readily available and its use unregulated. To examine the demographics, clinical and electrophysiological findings of patients presenting with neurological complications of N2 O abuse, and thus inform clinicians and public health decision-makers of the significant public health concerns of this increasing practice. Consecutive patients presenting to a tertiary referral metropolitan hospital were included in this series. Patients were identified by a search of discharge summaries of patients admitted with acute or subacute neuropathy or myelopathy and a history of N2 O abuse, and from the electrophysiology database. Thirteen patients were identified, most presenting with subacute paraesthesia, sensory ataxia and lower limb weakness. Eleven had low serum vitamin B12 . Spinal magnetic resonance imaging was consistent with subacute combined degeneration in eight. Nerve conduction studies revealed a motor or sensorimotor axonal neuropathy (three with motor predominance). There was a bimodal demographic distribution consisting of socially isolated, international university students and local residents with a history of mental illness and polydrug abuse. Recreational N2 O use is an emerging health problem in Australia. International university students and patients with pre-existing mental illness or polydrug use appear to be at increased risk. A severe motor neuropathy may emerge following vitamin B12 replacement. Public health measures are required to limit the availability of N2 O and to educate adolescents and young adults about the potential for significant harm.

Concurrent Radiation Therapy With the Antibody-Drug Conjugates Brentuximab Vedotin and Polatuzumab Vedotin

Brentuximab vedotin (BV) and polatuzumab vedotin (PV) are antibody-drug conjugates targeting CD30 and CD79B, respectively, approved for the treatment of select T- and B-cell lymphomas. Safety data to inform the use of concurrent radiation therapy (CRT) with BV or PV is lacking.We retrospectively reviewed 31 patients (pts) who received CRT with BV or PV from 5/2018 to 1/2021. We defined CRT as infusion within 3 weeks prior to or concurrent with RT. Timing of toxicity (CTCAE v5.0) was classified as pre-RT (within 1 month prior to RT), acute (start to 1 month post-RT), and subacute (2-3 months following RT), censored at subsequent systemic therapy. Statistics were performed using Mann-Whitney U and Chi-squared tests.Of 31 pts, 20 (65%) received BV and 11 (35%) received PV. Median age at CRT was 55 (range 27-88), and 14 pts were female (45%). 26 pts (84%) had stage III-IV disease at the time of CRT. The most common diagnoses were mycosis fungoides (12 pts, 39%; 7 with large cell transformation) and diffuse large B cell lymphoma (10 pts, 32%). Pts received a median of 4 lines of prior systemic therapy (range 0-8). 22 pts received prior RT courses (median 1, range 1-6). Fourteen pts received combination regimens with BV or PV: bendamustine and rituximab (R) (5, 16%); cyclophosphamide (C) (± R) (3, 10%); R alone (5, 16%); and C with doxorubicin (1, 3%). Eleven pts (35%) were treated with electrons targeting skin, with a median dose of 12 Gy (range 4-32). Twenty pts (65%) were treated with photons to 32 sites, with a median dose of 25 Gy (range 9-44); treatment sites included the spine (14 pts, 45%), abdomen/pelvis (9 pts, 29%), and brain (3 pts, 10%). Median percent bone marrow (BM) treated was 6.6 (range 0-18.3). The rate of grade 2 or higher (G2+) hematologic toxicity (HT) was 45% (14/31) pre-CRT vs. 79% (23/29) in the acute setting (P = 0.044) and 71% (10/14) in the subacute setting (P = 0.29). There was no significant change in acute or subacute pain, fatigue, diarrhea, neuropathy, or hepatotoxicity following CRT. Acute G2+ HT was associated with pre-RT G2+ HT (P = 0.019) and more lines of prior systemic therapy (P = 0.011). Percentage of BM irradiated was not significantly associated with acute G2+ HT (P = 0.09). Age, concurrent chemotherapy with BV or PV, prior RT courses, RT dose, and RT modality were not associated with G2+ HT. Six pts (19%) were bridged to stem cell transplant at a median of 26 days (IQR 16-52). 12 patients (39%) received subsequent systemic therapy for progression at a median of 81 days (IQR 25-87). Median time to progression or last follow-up was 72 days (IQR 20-113). At last follow-up, 18 pts (58%) were deceased; median overall survival from CRT was 177 days (95% CI 92-263).CRT with BV or PV was overall well tolerated. We observed HT, particularly in patients with cytopenias prior to RT. Care should be taken during RT planning to reduce this risk if possible.

Multiple Mononeuropathy in Churg-Strauss Syndrome Presenting as a Subacute Ascending Polineuropathy: A Case Report

Multiple mononeuropathy is not unusual in Churg-Strauss Syndrome. Presenting symptoms may be subacute and the differential diagnosis became complicated, particularly when neuropathy is the sole manifestation of disease. We report a clinical case of an adult man hospitalized complaining symptoms of subacute neuropathy succes-sively recognized as multiple mononeuropathy. Histological examination of sural nerve showed the evidence of systemic necrotizing vasculitis with eosinophils infiltration, confirming the diagnosis of CSS. Clinical and neuro-physiological findings are discussed.

Paraneoplastic Neurological Syndromes: Study of Prevalence in a Province of the Lombardy Region, Italy.

Paraneoplastic neurological syndromes (PNSs) are a heterogeneous group of rare immune-mediated diseases associated with cancer. The aim of this study was to investigate the prevalence of PNSs in the province of Brescia. PNS prevalence was calculated using the Lombardy regional hospital admission records from 1998 to 2003. We used the website “Epidemiologic and Economic Atlas of Hospital Activities in Lombardy” and the “International Statistical Classification of Diseases and Related Health Problems”. In the province of Brescia, we found 54 cases of PNSs, 29 with subacute neuropathies, five with paraneoplastic cerebellar degeneration and 20 with encephalomyelitis. Peripheral nervous system diseases were the most frequent neurological disorders. In Lombardy, the number of PNS patients admitted was 322 (133 with encephalomyelitis, 21 with paraneoplastic cerebellar degeneration, 166 with polyneuropathies and two with optic degeneration). In Lombardy, the prevalence of PNSs was 25 in 100,000 hospital admissions and 5.92 in 100,000 for the Lombardy population. Our results show a discrete presence of PNS patients in the province of Brescia and in the Lombardy region as a whole.

Neuromuscular complications following targeted therapy in cancer patients: beyond the immune checkpoint inhibitors. Case reports and review of the literature

IntroductionIn the last years, many new drugs have been developed targeting different oncology pathways, overall improving both quality of life and survival in several malignancies. However, the increase of those therapies is associated with novel toxicities, mainly immune-related adverse events (irAEs), never observed before. Different irAEs are now well characterized, and, among them, neuromuscular complications, following immune checkpoint inhibitor (ICPi) therapy, are increasingly studied and described. However, there are also neurological complications related to the use of other targeted therapies, less known and probably underestimated. Herein we describe two oncological patients who developed neuromuscular diseases after administration of targeted therapies, different from ICPi.Case reportsThe first patient was treated with the combination of Vemurafenib and Cobimetinib, BRAF and MEK inhibitors, respectively, for a cutaneous melanoma. One year after the beginning of the combined treatment, she developed a sub-acute motor neuropathy with predominant cranial nerve involvement. She was successfully treated with methylprednisolone. The second patient received therapy with Imatinib, tyrosine kinase inhibitor and precursor of the targeted therapy, for a gastrointestinal stromal tumour. Few days after the first administration, he developed generalized myasthenia gravis with respiratory failure. Clinical remission was obtained with plasma-exchange, intravenous immunoglobulins and steroids.Discussion and ConclusionWe strengthen the relevance of neuromuscular complications which may occur long after treatment start or in patients receiving not only the latest ICPi but also “older” and apparently better-known targeted therapies. Also in the latter cases, an immune-mediated “off-target” pathogenic mechanism can be hypothesized, and consequences can be life threatening, if not promptly diagnosed and appropriately managed.

Lumbosacral Radiculoplexus Neuropathy: A Case Series

Lumbosacral radiculoplexus neuropathy (LRPN) is an acute or subacute painful neuropathy that is probably underrecognized; in diabetic patients, this

Chronic relapsing inflammatory optic neuropathy: a literature review

Chronic relapsing inflammatory optic neuropathy (CRION) is an inflammatory disease characterized by painful recurrent episodes of optic neuritis with clear response to steroids and relapses with treatment withdrawal. To performed a systematic review of the literature about CRION, since 2003 to present in medical database. We excluded pediatric or animal research articles. Search terms: CRION, chronic relapsing inflammatory optic neuropathy, recurrent optic neuritis, steroid dependent optic neuritis, and immunosuppression dependent optic neuritis. CRION is a relapsing optic neuritis of unknown aetiology. The strong response to corticosteroids to avoid recurrence suggests that it might be an immune-mediated disease. CRION typically presents as a subacute and recurrent optic neuropathy with severe visual loss. The principal differential diagnoses are the demyelinating (multiple sclerosis, neuromyelitis optica spectrum disorders and anti-MOG), systemic (mostly sarcoidosis) and infectious diseases. CRION has a dramatic and dependent corticoids response; to avoid adverse events, we use immunosuppressive treatment in long-term. CRION is a rare, recurrent and cortico-dependent disease of optic nerve. An early diagnosis and accuracy treatment will improve the prognosis.

S40. Acute and subacute motor neuropathy in type II diabetic patients

Introduction Diabetic neuropathy is the most common complication of diabetes mellitus (DM), affecting as many as 50% of patients with type 1 and type 2 DM. There are four main types of diabetic neuropathy; Peripheral neuropathy, autonomic neuropathy, radiculo-plexus neuropathy (diabetic-amyotrophy) and mononeuropathy. The aim of the study was to describe the clinical presentation, electrophysiological investigations and in the future the immunological profile of such patients. Methods Seven type II diabetic patients were selected for the study. Ethical approval and patients’ informed consent have been obtained. They are all presented with acute and subacute onset of predominantly lower limb distal muscle weakness, on occasion proximal. The onset of this weakness was not preceded by upper respiratory tract infection, diarrhea or febrile illness. Results On examination there was symmetrical weakness of the distal foot flexors and extensors (power ranges 0–3), lower limb reflexes varies from diminished to absent. Tone was normal in the majority and flaccid in some of the patients. All modalities of sensation are intact except for disturbance of light touch in two patients. All patients were investigated for other causes of neuropathies. Neurophysiological investigations revealed signs of predominant demyelination with axonal degeneration. Patients showed very good response to immunoglobulin infusion (i.e. recovery of weakness after one to three months). Immunological studies are undergoing. Conclusion This was a preliminary report of a very uncommon presentation of acute motor neuropathy in diabetic patients. The cause possibly might be immune-mediated nerve damage but this has to be confirmed when we recruit more patients with detailed immune-profile studies.

Monofocal femoral subacute neuropathy as a key diagnostic element in a case of sigmoid neoplasm

Monofocal femoral subacute neuropathy as a key diagnostic element in a case of sigmoid neoplasm

50. Peripheral neuropathy associated with Duodopa infusion: neurophysiological retrospective study

Subacute and chronic peripheral neuropathies (PN) have been reported in Parkinson’s disease (PD) patients treated with levodopa/carbidopa intestinal gel infusion (Duodopa), but only one study evaluated a long term follow up. We performed a retrospective electrophysiological study of 23 PD patients treated with Duodopa with a follow up period of 18 months. The electrophysiological assessments of 23 patients have been retrospectically collected and evaluated at baseline (before Duodopa infusion) and at 6, 12 and 18 months. Nerve conduction studies were obtained for the bilateral median, ulnar, tibial and peroneal motor nerves and for the bilateral median, ulnar and sural sensory nerves. During a follow-up period of 18 months, a statistically significant decrease in mean sural SAP amplitude was recorded. At baseline 5/23 patients showed PN. During the follow up, one patient developed a subacute PN and two patients developed a sensory-motor PN. Duodopa infusion was immediately halted in the subacute case, while the infusion therapy was not interrupted in chronic forms. All patients were supplemented with vitamin B12 and folate. Serial electrophysiological evaluations are mandatory in patients treated with Duodopa, given the possible risk of PN.

Peripheral neuropathy associated with levodopa-carbidopa intestinal infusion: a long-term prospective assessment.

Subacute and chronic peripheral neuropathies (PNP) have been reported in Parkinson's disease (PD) patients treated with levodopa/carbidopa intestinal gel infusion (LCIG), although several aspects of their incidence and pathogenesis still remain to be clarified. This study main objective is to prospectively report the 2-year incidence of PNP in patients treated with LCIG. The clinical, hematological, nutritional and electrophysiological assessments of 33 consecutive patients have been prospectively collected and evaluated. At baseline (before the start of LCIG therapy), 3/33 (9%) patients showed symptomatic PNP and 7/33 (21%) subclinical PNP. During a follow-up of 24.36 ± 12.18 months, 2/23 patients with normal baseline clinical-electrophysiological assessment developed a subacute PNP, 2/23 developed a chronic PNP and 7/23 developed a subclinical PNP. LCIG was immediately halted in the subacute cases, while the infusion therapy was not interrupted in chronic and subclinical forms. All PNP were supplemented with vitamin B1 and B12, showing a clinical improvement and/or substantial stability at the following evaluations. Higher levodopa-equivalent daily dose (P: 0.024) and homocysteine levels (P: 0.041) were found in chronic PNP, while no correlations were observed with vitamin B12, folate and UPDRS values. A trend towards BMI reduction was observed in both PNP and unaffected subjects and one patient developed a symptomatic PNP associated with a relevant weight loss. Serial clinical-electrophysiological evaluations are mandatory in patients treated with LCIG, given the possible risk of subacute and chronic PNP. No clear causative factors has been recognized in the subacute forms, whilst homocysteine-mediated neurotoxicity seems to underlie the pathogenesis of chronic forms.

Acute and subacute motor neuropathy in diabetic patients case reports

Acute and subacute motor neuropathy in diabetic patients case reports

Photodynamic Sensory Neuropathy in a Patient Treated With St John's Wort.

To the Editor: The popular herbal preparation St John’s wort is widely used to treat mild to moderate depression. The chemical composition of St John’s wort has been well studied.1 Hypericin, an active ingredient in St John’s wort, has many psychoactive and photodynamic properties, and photosensitivity is one of its possible side effects.2 This report highlights a case of allodynia induced by St John’s wort following sun exposure. Case report: Ms A, a 40-year-old woman, presented to a private family practice office with depressive symptoms. She was diagnosed with mild to moderate depression after scoring 5 on the 9-item Patient Health Questionnaire.3 Ms A had read about some over-the-counter supplements and decided to try the herbal medication St John’s wort 500 mg twice daily before starting any other treatment options. During the follow-up visit 4 weeks after initiating therapy with St John’s wort, Ms A noted improvement of her depressive symptoms but complained of a tingling sensation in her hands whenever she washed them with cold water. This sensation began during the fourth week of therapy after she started working long hours in the sun. The physical examination revealed no skin erythema or burning. The use of a cold tuning fork on the hands produced a tingling sensation and discomfort; light touch did not provoke pain. The symptoms were restricted to the hands. There were no motor or other sensory disturbances, and she had normal peripheral reflexes. Following a review of the literature, Ms A was diagnosed with subacute toxic neuropathy on the basis of a report by Bove,4 who described a patient who experienced similar symptoms following ingestion of St John’s wort. St John’s wort was discontinued, and Ms A’s symptoms started improving after 1 week, with complete resolution of symptoms within 3 weeks of stopping the herb. In a case report, Bove4 suggested that possible demyelination of cutaneous axons caused a patient’s symptoms, but the lack of any other motor or sensory involvement might suggest a different etiology. One possible suggestion would be the activation of the transient receptor potential cation channel, subfamily A, member 1 (TRPA1), a nociceptive ion channel expressed in the unmyelinated c fibers in the sensory neurons in the skin. TRPA1 is considered a key player in acute and chronic (neuropathic) pain, and it is activated by noxious cold and chemical compounds.5 Hypericin activation occurs when the substance is exposed to ultraviolet A. This exposure leads to the release of reactive oxygen radicals,6 which have the potential to activate TRPA1, leading to painful or burning sensations in the light-exposed areas, mimicking symptoms occurring during photodynamic therapy.5 Photosensitivity can occur with the use of St John’s wort, but clinicians also should be aware of possible photodynamic activation of sensory neurons with sunlight exposure.

The Ultrasound pattern sum score – UPSS. A new method to differentiate acute and subacute neuropathies using ultrasound of the peripheral nerves

ObjectiveUltrasound differentiation of neuropathies is a great challenge. We, therefore, suggest a standardized score to operationalize differentiation between several acute and subacute onset neuropathies. MethodWe retrospectively analyzed the ultrasound data of 61 patients with acute or subacute neuropathies, e.g. chronic immune-mediated neuropathies, Guillain–Barré syndrome (GBS), and axonal/vasculitic neuropathies. We compared these data to 28 healthy controls. Based on these results an ultrasound pattern sum score (UPSS) with three sub-scores (UPS-A for the sensorimotor nerves, UPS-B for the cervical roots and the vagal nerve and UPS-C for the sural nerve) was developed. Afterwards, the applicability of the score was prospectively validated in 10 patients with chronic neuropathies and in 14 patients with unknown acute and subacute PNP before performing additional tests. ResultsUPS-A and UPSS were significantly higher in CIDP than in other neuropathies and controls (p<0.001). UPS-B was significantly more often pathologic in GBS than in CIDP and other neuropathies (p<0.001). Using receiver operation characteristics curve analysis boundary values for each score were defined. Positive predictive value (PPV) of these scores for CIDP and GBS was >85%. Vasculitic neuropathies showed an intermediate type of UPSS compared to other axonal neuropathies (p<0.001). In the prospective application the pattern score could be used with good accuracy in several types of neuropathy. ConclusionUPS-A and UPSS operationalize to diagnose acute and subacute-onset CIDP and its variants with high sensitivity, specificity, and PPV. An increased UPS-B with normal UPSS and other sub scores may point to the diagnosis of GBS with high PPV and enables the differentiation from CIDP. SignificanceUsing the UPSS and its sub-scores gives a new diagnostic power to the method of the peripheral nerve ultrasound.

Rare neurologic complication of bariatric surgery: acute motor axonal neuropathy (AMAN), a severe motor axonal form of the Guillain Barré syndrome

Bariatric surgery (BS) procedures are more and more common and have various neurologic complications including acute polyradiculoneuropathies [1–4]. These patients tend to have axonal degeneration rather than demyelination, and normal cerebrospinal fluid (CSF) protein levels [2]. These polyradiculoneuropathies, rapidly progressive, have been described between 6 weeks and 2 years after surgery [2]. Symptoms include pain in the feet or lower limbs, with ascending paresthesias, progressive leg weakness with ataxia, and areflexia. BS neurologic complications are usually related to micronutrients deficiencies secondary to malabsorption after surgery [1]. But immune and inflammatory processes may play a part in the pathogenesis of neuronal injury, as suggested by data from sural nerve biopsies showing inflammatory cell infiltrates in patients with acute or subacute neuropathies or radiculoplexoneuropathies post-BS [5]. We report a case where the presence of anti-GM1, anti-MAG, anti-GD1a antibodies in a patient with acute motor axonal neuropathy (AMAN), 5 months after BS supports this immunologic hypothesis.

Thyrotoxic neuropathy; an under recognized condition: A clinical vignette

Neurological sequelae such as neuromuscular or primary muscle disorders are well recognized complications of hyperthyroidism. However, the association of neuropathy with thyrotoxicosis is uncommon. Thyrotoxic neuropathy or Basedow's paraplegia is a rarely reported entity, which was first described by Charcot in 1889. We are reporting the case of a middle-aged man with subacute distal neuropathy as the presenting manifestation of thyrotoxicosis which improved on antithyroid treatment. Peripheral neuropathy in hyperthyroidism is underdiagnosed and may be found even in patients with mild thyrotoxicosis. Thyroid function tests can be helpful in the diagnosis of this treatable neuropathy in such cases and hence should be included in the routine workup in patients with peripheral neuropathy.

Paraneoplastic neurological syndromes in lymphoid neoplasms: a clinical and laboratorial challenge.

Paraneoplastic neurological syndromes in lymphoid neoplasms: a clinical and laboratorial challenge.

Autonomic Involvement in Subacute and Chronic Immune-Mediated Neuropathies

Autonomic function can be impaired in many disorders in which sympathetic, parasympathetic, and enteric arms of the autonomic nervous system are affected. Signs and symptoms of autonomic involvement are related to impairment of cardiovascular, gastrointestinal, urogenital, thermoregulatory, sudomotor, and pupillomotor autonomic functions. Availability of noninvasive, sensitive, and reproducible tests can help to recognize these disorders and to better understand specific mechanisms of some, potentially treatable, immune-mediated autonomic neuropathies. This paper describes autonomic involvement in immune-mediated neuropathies with a subacute or chronic course.