Jinny Tavee

Small fiber neuropathy: A burning problem

Small fiber neuropathy is increasingly being recognized as a major cause of painful burning sensations in the feet, especially in the elderly. Although strength remains preserved throughout the course of the disease, the pain and paresthesias are often disabling. Diabetes mellitus is the most common identifiable cause of small fiber neuropathy, and impaired oral glucose tolerance and individual components of the metabolic syndrome are often associated with it. Some cases, however, are idiopathic. Skin biopsy (with an evaluation of the density of intraepidermal nerve fibers) and tests of autonomic nerve function are useful for the diagnosis. Management involves controlling pain and identifying and aggressively treating the underlying cause.

Response to intravenous immunoglobulin in Anti-Yo associated paraneoplastic cerebellar degeneration: case report and review of the literature

Paraneoplastic cerebellar degeneration (PCD) is a debilitating neuro-degenerative disease associated with antibodies directed against the purkinje cells of the cerebellum. Treatment using chemotherapy or other treatment of the primary tumor to various immunologically directed therapies has been attempted but outcomes have been poor. We discuss a patient with ovarian carcinoma and PCD seen in our institution who showed a marked beneficial response to intravenous immunoglobulin (IVIG) and methylprednisolone. A Medline search from 1966-2002 produced fifteen cases of PCD confirmed by antibody testing that were treated with IVIG, either alone, or with a combination of other therapies. The clinical characteristics and treatment responses of these patients are analyzed in this review. Most patients that were treated with IVIG and had what was defined as a good response were treated within one month of symptoms. Patients treated between one month and three months often had stable disease and patients treated after three months of symptoms usually had a poor outcome. Early treatment with sufficiently high doses of IVIG seems to provide a better chance of treatment success. The additional benefit of early high dose intravenous methylprednisolone is unclear. Due to the devastating nature of the disease, a trial of IVIG and steroids is warranted as early as possible in a dose of 2g/kg to any patient with a clinical picture of PCD and positive antibodies.

Severe postictal laryngospasm as a potential mechanism for sudden unexpected death in epilepsy: a near-miss in an EMU

A 42‐year‐old man with refractory epilepsy experienced a 1‐min generalized tonic–clonic seizure followed by persistent inspiratory stridor and cyanosis while being monitored in our epilepsy monitoring unit (EMU). Although his cardiac parameters remained stable throughout the event, the patient’s respiratory status rapidly declined, despite the urgent administration of oxygen via bag‐valve‐mask. He was subsequently intubated by the emergency code team, who noted severe laryngospasm while trying to insert the endotracheal tube. The patient was successfully resuscitated. This monitored case demonstrates that postictal laryngospasm may represent another potential cause of sudden unexpected death in epilepsy (SUDEP).

Efficacy of intravenous immunoglobulin for small fiber neuropathy associated with sarcoidosis

BACKGROUND Small fiber neuropathy (SFN) is commonly associated with sarcoidosis and can cause significant morbidity to afflicted patients. The appropriate treatment of this condition, when associated with sarcoidosis, is not well established. METHODS Descriptive case series of three patients with sarcoidosis and SFN. The presenting clinical features, skin biopsy results, autonomic reflex screen and quantitative sudomotor axon reflex testing (QSART) findings, and response to therapy are delineated. RESULTS We describe three patients with biopsy-proven sarcoidosis who developed intractable neuropathic pain and/or symptoms related to associated autonomic dysfunction despite treatment with various immunosuppressive medications and narcotic analgesics. QSART showed evidence of a postganglionic sudomotor abnormality in one patient and was normal in the other two. Skin biopsy findings were abnormal, demonstrating a non-length-dependent sensory SFN in all three patients. Painful neuropathic symptoms, as well as symptoms related to dysautonomia from SFN responded significantly to treatment with intravenous immunoglobulin (IVIG). CONCLUSION IVIG appears to be effective in relieving symptoms from SFN associated with sarcoidosis, suggesting an underlying immune mechanism. Larger prospective, controlled studies would be needed to confirm this response to IVIG and to further elucidate the underlying pathobiology behind this association with sarcoidosis.

Sarcoidosis and Small-fiber Neuropathy

Chronic pain is one of the most commonly reported symptoms among sarcoidosis patients. Not only does it significantly affect quality of life, but it also is a source of frustration for both the patient and physician because the etiology for pain often is unknown. Although patients typically complain of neuropathic-type pain, nerve conduction studies and other conventional diagnostic procedures frequently fail to reveal objective evidence of neurologic disease. However, in recent years, the growing use of specialized tests such as skin biopsy and sudomotor testing has helped to establish the diagnosis of small-fiber neuropathy as the cause of pain in these patients via objective and quantifiable means. Management of sarcoidosis small-fiber neuropathy should consist of target-directed treatment of the underlying disease and appropriate symptomatic therapy.

Spinal cord neurosarcoidosis

Background:Spinal cord neurosarcoidosis (SN) is problematic to diagnose because it mimics other inflammatory neurologic diseases. The authors report the clinical features of 29 SN cases. Methods:They retrospectively reviewed the medical records of 29 histologically proven sarcoidosis patients with spinal cord involvement seen at 3 university medical centers. They collected clinical data including laboratory and radiological findings. Clinical outcomes were assessed retrospectively using the modified Rankin scale. Results:The cohort included high number of African Americans (16/29, 55%). The lung and intrathoracic lymph nodes were the most common confirmatory biopsy sites (18/29, 62%), whereas the spinal cord was a relatively uncommon one (4/29, 14%). The most common presenting symptoms were lower extremity weakness and paresthesias. Thoracic segment was most frequently involved (21/27, 78%). Lesions were mostly intramedullary (22/27, 81%), although nearly half involved the leptomeninges (13/27, 48%). The average size of a lesion spanned 3.9 spine segments (range, 1–9); 17 of 22 (77%) intramedullary patients had ≥3 spine segments involved. Angiotensin-converting enzyme levels in cerebrospinal fluid were elevated in only 2 of 11 (18%) patients. All patients received glucocorticosteroids. Additional immune-modulating agents were used in 24 of 29 (83%) patients. Scores on the modified Rankin scale at the final follow-up visit were improved. Conclusions:Most SN cases were diagnosed indirectly based on extraneural tissue biopsy. Extended spinal cord lesion (≥3 spine segments) may be useful to distinguish SN from multiple sclerosis. Cerebrospinal fluid analysis was of limited value. Most patients experienced clinical improvement with immunosuppressive treatment, but many required combination therapy.

Effects of Meditation on Pain and Quality of Life in Multiple Sclerosis and Peripheral Neuropathy: A Pilot Study

The objective of this study was to determine whether meditation affects pain and quality of life in people with multiple sclerosis (MS) and peripheral neuropathy (PN). A total of 22 patients (10 with MS, 12 with PN) participated in a weekly meditation class over a 2-month period. A total of 18 controls (7 with MS, 11 with PN) received standard care. Primary outcome assessments were based on the 36-item Short Form Health Status Survey (SF-36) and a visual analogue scale (VAS) for pain at baseline and at 2 months. Secondary outcome measures included the Neuropathy Impairment Score (NIS) for PN patients and the Patient-Determined Disease Steps (PDDS) questionnaire and 5-item Modified Fatigue Impact Scale (MFIS-5) for MS patients. After 2 months, study participants who practiced meditation reported an improvement in pain on the VAS (P = .035 combined group), summed physical health scores on the SF-36 (P = .011 MS, P = .014 PN), summed mental health scores (P = .02 combined group), vitality (P = .005 combined group), and physical role (P = .003 combined group). A significant improvement was also observed for bodily pain (P = .031) in MS patients. In contrast, no significant differences before and after the intervention were observed for controls. Regarding the secondary measure of fatigue, improved scores for the cognitive and psychosocial components of the MFIS were noted in MS patients in the intervention group (P = .037, P = .032). No statistically significant changes were observed in the NIS for PN patients or in PDDS scores for MS patients. Meditation may be helpful in reducing pain and improving quality of life in patients with MS and PN. The lack of changes seen in mobility (MS) and sensorimotor deficits (PN) suggests that meditation may not affect the overall clinical course.

Cibinetide Improves Corneal Nerve Fiber Abundance in Patients With Sarcoidosis-Associated Small Nerve Fiber Loss and Neuropathic Pain

Purpose Sarcoidosis frequently is complicated by small nerve fiber loss (SNFL), which can be quantified using corneal confocal microscopy (CCM). Prior studies suggest that the innate repair receptor agonist cibinetide reverses corneal nerve loss. This phase 2b, 28-day, randomized trial of 64 subjects with sarcoid-associated SNFL and neuropathic pain assessed the effect of cibinetide on corneal nerve fiber area (CNFA) and regenerating intraepidermal fibers (GAP-43+) as surrogate endpoints for disease modification, pain severity, and functional capacity (6-minute walk test [6MWT]). Methods Cibinetide (1, 4, or 8 mg/day) was compared to placebo. The primary study endpoint was a change in CNFA at 28 days. Results The placebo-corrected mean change from baseline CNFA (μm2) at day 28 was 109 (95% confidence interval [CI], -429, 647), 697 (159, 1236; P = 0.012), and 431 (-130, 992) in the 1, 4, and 8 mg groups, respectively. Intraepidermal GAP-43+ fibers increased in the 4 mg group (P = 0.035). Further, changes in CNFA correlated with changes in GAP-43+ (ρ = 0.575; P = 0.025) and 6MWT (ρ = 0.645; P = 0.009). Pain improved significantly in all groups, with subjects having moderate-severe pain reporting a clinically meaningful placebo-corrected decrease in pain intensity in the 4 mg group (P = 0.157). Conclusions Cibinetide significantly increased small nerve fiber abundance in the cornea and skin, consistent with a disease modifying effect. The relationships between CNFA and other clinical measures of disease support its use as a surrogate endpoint to assess potential disease modifying therapies for neuropathy.

Pitfalls in the electrodiagnostic studies of sacral plexopathies.

This retrospective review characterizes the electrodiagnostic (EDX) features and etiologies of sacral plexopathies (SPs) and discusses difficulties in their identification. The EDX findings of 171 clinically suspected SPs were reviewed using the following criteria: reduced/absent sensory nerve action potentials (SNAPs) of the sural or superficial peroneal nerve, denervation of plexus‐innervated muscles, and the absence of paraspinal denervation. Sixty cases localized unequivocally to the sacral plexus. The majority were cancer‐related, followed by traumatic, idiopathic, and iatrogenic causes. Final diagnoses in the remaining 111 cases were indeterminate. Lesions localized to either the plexus or L4–5, S1 roots in 52 cases, the plexus or sciatic nerve in 32 cases, and were equally compatible with an SP, sciatic neuropathy, or radiculopathy in 27 cases. Findings in the EDX evaluation of SPs are often complex and difficult to localize to a specific site due to multiple complicating factors. Frequently, SPs cannot be diagnosed definitively by EDX assessment alone. Muscle Nerve, 2007

Sural sensory nerve action potential, epidermal nerve fiber density, and quantitative sudomotor axon reflex in the healthy elderly

Introduction: Polyneuropathy evaluation in older patients is often challenging due to conflicting data regarding normative values for peripheral nerve testing. Methods: We characterized the results of sural nerve conduction studies, intraepidermal nerve fiber density (IENFD), and quantitative sudomotor axon reflex testing (QSART) in a prospective study of 50 healthy subjects aged ≥60 years. Results: Of the 50 subjects, 48 (96%) had an obtainable sural sensory nerve action potential (SNAP). Using quantile regression, we estimated the lower limit of normal (LLN) for sural amplitudes to be 3 μV for patients 60–70 years, 1 μV for those 70–74 years, and <1 μV (absent) for those ≥75 years of age. IENFD and QSART volume were reduced with advancing age, although IENFD was lower in men and QSART volume was lower in women. Conclusions: We propose that an absent sural SNAP in patients up to 75 years of age should be considered abnormal. Our findings also support age‐ and gender‐stratified normative data for IENFD and QSART. Muscle Nerve 49:564–569, 2014