Acute and Chronic Demyelinating Neuropathies After COVID-19 Vaccination: A Report of 4 Cases.

OBJECTIVES: To report demyelinating neuropathies after COVID-19 vaccination. METHODS: Case report. RESULTS: Four cases of demyelinating neuropathies after COVID-19 vaccination were identified at the University of Nebraska Medical Center from May to September 2021. Three were male and 1 was a female, ages 26-64 years. Three cases received Pfizer-BioNTech vaccine and 1 Johnson & Johnson. Symptom onset ranged from 2 to 21 days after vaccination. Two cases had progressive limb weakness, 3 had facial diplegia, and all had sensory symptoms and areflexia. The diagnosis was acute inflammatory demyelinating polyneuropathy in 1 case and chronic inflammatory demyelinating polyradiculoneuropathy in 3. All cases received treatment with intravenous immunoglobulin, with significant improvement in 3 of 4 who had a long-term outpatient follow-up. CONCLUSIONS: Continued identification and reporting of cases of demyelinating neuropathies after COVID-19 vaccination is essential to determine whether a causative association is present.

Electrodiagnostic assessment of the autonomic nervous system: A consensus statement endorsed by the American Autonomic Society, American Academy of Neurology, and the International Federation of Clinical Neurophysiology.

Evaluation of disorders of the autonomic nervous system is both an art and a science, calling upon the physician's most astute clinical skills as well as knowledge of autonomic neurology and physiology. Over the last three decades, the development of noninvasive clinical tests that assess the function of autonomic nerves, the validation and standardization of these tests, and the growth of a large body of literature characterizing test results in patients with autonomic disorders have equipped clinical practice further with a valuable set of objective tools to assist diagnosis and prognosis. This review, based on current evidence, outlines an international expert consensus set of recommendations to guide clinical electrodiagnostic autonomic testing. Grading and localization of autonomic deficits incorporates scores from sympathetic cardiovascular adrenergic, parasympathetic cardiovagal, and sudomotor testing, as no single test alone is sufficient to diagnose the degree or distribution of autonomic failure. The composite autonomic severity score (CASS) is a useful score of autonomic failure that is normalized for age and gender. Valid indications for autonomic testing include generalized autonomic failure, regional or selective system syndromes of autonomic impairment, peripheral autonomic neuropathy and ganglionopathy, small fiber neuropathy, orthostatic hypotension, orthostatic intolerance, syncope, neurodegenerative disorders, autonomic hyperactivity, and anhidrosis.

Patient Assisted Intervention for Neuropathy: Comparison of Treatment in Real Life Situations (PAIN-CONTRoLS): Bayesian Adaptive Comparative Effectiveness Randomized Trial.

Importance: Cryptogenic sensory polyneuropathy (CSPN) is a common generalized slowly progressive neuropathy, second in prevalence only to diabetic neuropathy. Most patients with CSPN have significant pain. Many medications have been tried for pain reduction in CSPN, including antiepileptics, antidepressants, and sodium channel blockers. There are no comparative studies that identify the most effective medication for pain reduction in CSPN. Objective: To determine which medication (pregabalin, duloxetine, nortriptyline, or mexiletine) is most effective for reducing neuropathic pain and best tolerated in patients with CSPN. Design, Setting, and Participants: From December 1, 2014, through October 20, 2017, a bayesian adaptive, open-label randomized clinical comparative effectiveness study of pain in 402 participants with CSPN was conducted at 40 neurology care clinics. The trial included response adaptive randomization. Participants were patients with CSPN who were 30 years or older, with a pain score of 4 or greater on a numerical rating scale (range, 0-10, with higher scores indicating a higher level of pain). Participant allocation to 1 of 4 drug groups used the utility function and treatment's sample size for response adaptation randomization. At each interim analysis, a decision was made to continue enrolling (up to 400 participants) or stop the whole trial for success (80% power). Patient engagement was maintained throughout the trial, which helped guide the study and identify ways to communicate and disseminate information. Analysis was performed from December 11, 2015, to January 19, 2018. Interventions: Participants were randomized to receive nortriptyline (n = 134), duloxetine (n = 126), pregabalin (n = 73), or mexiletine (n = 69). Main Outcomes and Measures: The primary outcome was a utility function that was a composite of the efficacy (participant reported pain reduction of ≥50% from baseline to week 12) and quit (participants who discontinued medication) rates. Results: Among the 402 participants (213 men [53.0%]; mean [SD] age, 60.1 [13.4] years; 343 White [85.3%]), the utility function of nortriptyline was 0.81 (95% bayesian credible interval [CrI], 0.69-0.93; 34 of 134 [25.4%] efficacious; and 51 of 134 [38.1%] quit), of duloxetine was 0.80 (95% CrI, 0.68-0.92; 29 of 126 [23.0%] efficacious; and 47 of 126 [37.3%] quit), pregabalin was 0.69 (95% CrI, 0.55-0.84; 11 of 73 [15.1%] efficacious; and 31 of 73 [42.5%] quit), and mexiletine was 0.58 (95% CrI, 0.42-0.75; 14 of 69 [20.3%] efficacious; and 40 of 69 [58.0%] quit). The probability each medication yielded the highest utility was 0.52 for nortriptyline, 0.43 for duloxetine, 0.05 for pregabalin, and 0.00 for mexiletine. Conclusions and Relevance: This study found that, although there was no clearly superior medication, nortriptyline and duloxetine outperformed pregabalin and mexiletine when pain reduction and undesirable adverse effects are combined to a single end point. Trial Registration: ClinicalTrials.gov Identifier: NCT02260388.

Peripheral Nervous System Involvement.

Peripheral nervous system involvement in primary systemic amyloidosis is another important organ involvement in the spectrum of this disease entity. Early recognition may lead to an earlier diagnosis and treatment with improvement in prognosis.

Prediabetes, diabetes, metabolic syndrome, and small fiber neuropathy.

INTRODUCTION: This study was conducted to evaluate the association between prediabetes (PD), elements of the metabolic syndrome (MetS), and small fiber neuropathy (SFN). METHODS: A total of 268 patients with SFN symptoms and normal electrophysiology underwent tests to assess small fibers. SFN was diagnosed based on abnormality of at least two among intraepidermal nerve fiber density (IEFND), quantitative sensory testing, and quantitative sudomotor axon reflex testing. RESULTS: There was no difference in IENFD or abnormal skin biopsy frequency between PD and normoglycemia (NG). However, IENFD was lower in people with diabetes mellitus (DM) than in those with NG. An association between HbA1C and IENFD was observed only if DM patients were included. Attributes of the MetS were more common in those with an abnormal skin biopsy but not among those with autonomic dysfunction or meeting SFN criteria. DISCUSSION: DM, but not PD alone, is associated with SFN. Other MetS elements appear to preferentially impact small fiber structure over function.

An altered spatiotemporal gait adjustment during a virtual obstacle crossing task in patients with diabetic peripheral neuropathy.

This study investigates spatiotemporal gait adjustments that occur while stepping over virtual obstacles during treadmill walking in people with/without diabetic peripheral neuropathy (DPN). Eleven adults with Type 2 diabetes mellitus, ten DPN, and 11 age-matched healthy adults (HTY) participated in this study. They stepped over forthcoming virtual obstacles during treadmill walking. Outcomes such as success rate, spatiotemporal gait characteristics during obstacle crossing, and correlations between these variables were evaluated. The results partially supported our hypotheses that when comparing with HTY and DM, people with DPN adopted a crossing strategy which decreased obstacle crossing success rate and maximal toe elevation, and increased stride time and stance time during virtual obstacle crossing. This might be due to the compromised somatosensory functions of their lower extremity which may increase the risk of falling. This study also found an inter-leg relationship which may be applied to future stepping or obstacle crossing training that incorporates both legs as a means for improving outcomes of the trailing leg during daily obstacle negotiation.

Inflammatory Diabetic Neuropathy: Helpful Diagnostic Parameters.

OBJECTIVES: Mild inflammatory diabetic neuropathies (IDNs) overlap with diabetic sensorimotor neuropathy (DPN) in clinical presentation and electrophysiological and laboratory tests. This study is to determine whether IDN can be differentiated from DPN by clinical features, electrophysiological, pathological, or laboratory tests. METHODS: Suspected IDN cases were identified by a subacute onset and progressive sensory or motor neuropathy in patients with diabetes. RESULTS: IDN occurred earlier in the course of diabetes mellitus and had higher prevalence of limb weakness, walking difficulty, and more severe electrophysiological abnormalities suggesting both demyelination and axonal loss. Sensory nerve biopsies in IDN showed perivascular inflammatory infiltrates, decreased fiber density, increased demyelination, and axonal degeneration. Most patients with IDN improved with immunotherapy. CONCLUSIONS: Features that favor IDN over DPN are limb weakness, more severe nerve conduction abnormalities, inflammatory infiltrates on nerve biopsy, and a favorable response to immunotherapy. A nerve biopsy can help establish an inflammatory cause.

Pure Autonomic Failure.

Pure autonomic failure (PAF) is a rare sporadic neurodegenerative autonomic disorder characterized by slowly progressive pan autonomic failure without other features of neurologic dysfunctions. The main clinical symptoms result from neurogenic orthostatic hypotension and urinary and gastrointestinal autonomic dysfunctions. Autonomic failure in PAF is caused by neuronal degeneration of pre- and postganglionic sympathetic and parasympathetic neurons in the thoracic spinal cord and paravertebral autonomic ganglia. The presence of Lewy bodies and α-synuclein deposits in these neural structures suggests that PAF is one of Lewy body synucleinopathies, examples of which include multiple system atrophy, Parkinson disease, and Lewy body disease. There is currently no specific treatment to stop progression in PAF. Management of autonomic symptoms is the mainstay of treatment and includes management of orthostatic hypotension and supine hypertension. The prognosis for survival of PAF is better than for the other synucleinopathies.

Vasculitic neuropathy following exposure to minocycline.

OBJECTIVE: To report 3 patients with minocycline-induced autoimmunity resulting in peripheral nerve vasculitis. METHODS: We report 3 patients who, during minocycline treatment for acne vulgaris, developed subacute onset of pain and weakness caused by vasculitis in single and multiple mononeuropathy patterns. RESULTS: Each patient underwent either a nerve or muscle biopsy that confirmed vasculitis. One patient additionally developed systemic symptoms (including fever, fatigue, and night sweats) and another had a posterior circulation stroke. Symptoms developed with either early or prolonged use of minocycline. Despite withdrawal of minocycline, patients needed long-term immunotherapy to gain neurologic improvement. CONCLUSIONS: Our findings suggest that the typical neuropathy associated with minocycline use is painful single or multiple mononeuropathy due to peripheral nerve vasculitis, which may also be accompanied by presumed CNS vasculitis (presenting as stroke).

Lumbosacral plexopathy.

PURPOSE OF REVIEW: This article provides an up-to-date review of the clinical features and pathogenesis of different types of lumbosacral plexopathy and a clinical approach to their evaluation and management. Often, the pathologic involvement is not limited to the plexus and also involves the root and nerve levels. These conditions are called lumbosacral radiculoplexus neuropathies. RECENT FINDINGS: The pathophysiology of diabetic and nondiabetic lumbosacral radiculoplexus neuropathy has been elucidated; it is ischemic injury due to a perivascular inflammatory process and microvasculitis. The clinical and neurophysiologic features of these two entities have been found to be similar, consisting of acute or subacute onset of pain and paresthesia followed by profound motor weakness asymmetrically involving the lower limbs and associated with weight loss. A lower limb and motor predominant neuropathy without pain also occurs in diabetes mellitus and has been shown to be a form of diabetic lumbosacral radiculoplexus neuropathy and not diabetic chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). The pathophysiology of some cases of postsurgical lumbosacral plexopathies has recently been shown also to be inflammatory from microvasculitis, and treatment with immunotherapy in a timely fashion may be desirable. SUMMARY: Many pathophysiologic processes, such as neoplastic, traumatic, infectious, radiation, and inflammatory/microvasculitic processes, can affect the lumbosacral plexus causing lumbosacral plexopathy. The clinical symptoms and signs depend on the part of the plexus involved and the temporal course. Management depends on the cause of the lumbosacral plexopathy. Many cases of lumbosacral plexopathy previously thought to be idiopathic have been shown to be caused by ischemic injury from microvasculitis; despite lack of evidence for efficacy in improving neurologic deficits, the authors of this article include immunotherapy in their management of patients with this condition.

Autonomic evaluation is independent of somatic evaluation for small fiber neuropathy.

BACKGROUND: The relationship between the autonomic reflex screening test (ARS) and measures of sensory function and structure (quantitative sensory testing (QST) and intraepidermal nerve fiber density (IENFD)) remains uncertain in patients with distal small fiber neuropathy (SFN). The aim of this study was to evaluate the correlations among a range of autonomic (quantitative sudomotor axon reflex test (QSART), cardiovagal and cardio adrenergic tests and the composite autonomic severity score (CASS)) and somatic sensory measures (QST of vibration, cooling and heat-pain thresholds and IENFD). METHOD: 122 patients with clinically suspected sensory neuropathy without motor weakness and with normal nerve conduction studies underwent blinded autonomic reflex screening test (ARS), quantitative sensory testing (QST) and skin biopsy (IENFD) for diagnosis of SFN. The relationship between autonomic and somatic sensory measures was assessed. RESULTS: There was no association between autonomic function measures (QSART volume, CASS_QSART, CASS_vagal, CASS_adrenergic or total CASS) and small fiber sensory measures (IENFD, cooling or heat-pain thresholds). Weak correlations were noted among some modalities of QST (vibration and cooling thresholds) and IENFD. DISCUSSION: Autonomic and sensory outcomes are independent (complementary) measures of distal SFN, and should where feasible be used concurrently in the evaluation of SFN.

Postsurgical inflammatory neuropathy: a report of five cases.

BACKGROUND: Clinical and pathologic descriptions of postsurgical inflammatory neuropathy have been reported but this condition is still under recognized. METHODS: We reviewed 5 cases of a biopsy-proven inflammatory neuropathy that occurred within 30 days after surgical procedures. These patients were seen at one center in a 2-year period. RESULTS: All patients developed neuropathy symptoms with time delay between the surgery and the neuropathy onset. In all, the symptoms progressed up to the time of evaluation. Electrophysiological studies revealed mononeuropathy or asymmetrical polyneuropathy with active denervation. Nerve biopsies showed ischemic injury and perivascular inflammatory collections in all cases. All patients were treated with intravenous methylprednisolone and four of them showed clinical improvement. The non-responsive patient did not receive immunotherapy until 2 years after neuropathy onset. CONCLUSIONS: The report illustrates that focal or asymmetrical neuropathy is typical of postsurgical inflammatory neuropathy and has a favorable outcome after intravenous corticosteroid treatment. The report underscores the importance for considering potentially treatable inflammatory neuropathies in the post-surgical setting.

Contribution of QSART to the diagnosis of small fiber neuropathy.

INTRODUCTION: We evaluated incorporation of the quantitative sudomotor axon reflex test (QSART) into the diagnostic criteria for small fiber neuropathy (SFN) as an addition to quantitative sensory testing (QST) and intraepidermal nerve fiber density (IENFD) testing. METHODS: One hundred one patients with clinically suspected SFN underwent QSART, QST, and skin biopsy. The diagnostic yield of existing SFN criteria in these patients was compared with criteria incorporating QSART. The new combined diagnostic criteria were evaluated. RESULTS: SFN was diagnosed in 38 of the 101 patients (38%) using current criteria. Addition of QSART existing SFN criteria resulted in an increased diagnostic yield to 67 patients (66%). Applying new SFN criteria requiring abnormality in at least 2 assessments among QSART, QST, and IENFD resulted in a diagnosis of SFN in 57 patients (56%). CONCLUSION: Assessment of both somatic and peripheral autonomic small nerve fibers enhances diagnostic criteria for SFN.

Selective infarction of the anterior genu fornices associated with giant cell arteritis.

We report a middle-aged woman presenting with acute confusion and anterograde amnesia. Magnetic resonance imaging revealed an acute infarction of the anterior genu fornices. Evaluation of an elevated erythrocyte sedimentation rate led to the diagnosis of giant cell arteritis (GCA). Cerebral infarction is a known complication of GCA; this is the first report of such an association with selective fornix infarction.

A case of fascioscapulohumeral muscular dystrophy misdiagnosed as Becker's muscular dystrophy for 20 years.

A 60-year-old man diagnosed clinically with Becker's muscular dystrophy 20 years ago by another physician presented with gradually progressive proximal muscle weakness since teenage years. Family history revealed a strong paternal familial inheritance pattern of similar distribution of weakness-face, forearm flexion, knee extension and foot dorsiflexion. Work-ups revealed B12 deficiency and allele 1 deletion in fascioscapulohumeral muscular dystrophy (FSHD) DNA testing. FSHD is the third most common muscular dystrophy. Clinical diagnosis is made from the distinctive pattern of weakness, autosomal-dominant inheritance, and confirmed by genetic testing. This case strongly demonstrates the importance of a thorough and careful clinical evaluation even in a case with a long standing diagnosis.

Vasculitic neuropathy associated with minocycline use.

INTRODUCTION: Minocycline is an antibiotic used for the treatment of acne. It has been associated with several autoimmune syndromes, including drug-induced lupus, autoimmune hepatitis, and vasculitis. METHOD AND RESULTS: We report a case of a 28-year-old previously healthy woman who developed a left sciatic mononeuropathy 2 weeks after starting minocycline for acne. Magnetic resonance imaging studies supported the localization. A biopsy of the left sural nerve revealed acute nerve large arteriole necrotizing vasculitis. Her condition improved after the withdrawal of minocycline and a course of treatment with methylprednisolone. CONCLUSION: This case provides further evidence that minocycline may induce a nonsystemic necrotizing vasculitis.

Treatment of diabetic and nondiabetic lumbosacral radiculoplexus neuropathy.

OPINION STATEMENT: Lumbosacral radiculoplexus neuropathy (LRPN) is a multifocal, asymmetric, painful neuropathic disorder affecting multiple levels of lumbosacral plexus, nerve roots, and distal nerves that emerge from the plexus. The disorder was first described in diabetic patients (DLRPN) and was later found to occur in nondiabetic patients as well. There have been debates as to the pathogenesis of DLRPN and LRPN. Recent detailed and extensive pathologic studies, however, have shown that the main pathogenesis is inflammation and microvasculitis affecting various components in the peripheral nerves, resulting in ischemic injury to the nerves. Even though studies on the natural history of this disorder have shown that the majority of patients recover within a few years after the attack without any treatment (although recovery is incomplete in many cases), it is a common practice, based on the pathophysiology and case series, to administer immunotherapy. Preliminary data from a controlled clinical trial failed to show significant improvement in outcomes measured by neurologic deficits (as judged by the Neuropathy Impairment Score) but did show improvement in symptoms (pain and positive sensory symptoms). Choices of immunotherapy include corticosteroids, intravenous immunoglobulin, plasma exchange, or a combination. Pain management, physical therapy, and treatment of depression remain mainstays for managing this disorder.

Adult-onset acid maltase deficiency with isolated axial muscle involvement.

INTRODUCTION: We report a patient with acid maltase deficiency who presented with subacute respiratory failure as the first symptom without significant extremity weakness. METHODS AND RESULTS: Electromyography of extremities was normal but showed myopathic changes and myotonic discharges limited to axial muscles only. Muscle biopsy confirmed the diagnosis. CONCLUSION: It is essential to examine axial muscles during electromyography if a patient presents with respiratory failure of unclear etiology even if the clinical examination does not show significant weakness in the extremities and electromyographic findings in the extremities are unremarkable.