Is electrodiagnosic testing for polyneuropathy overutilized?

Distal symmetric polyneuropathy (DSP) is one of the most common problems seen in clinical practice and one of the most frequent reasons for electrodiagnostic (EDx) testing. Most studies have supported the use of EDx testing for patients with suspected DSP. Some recent articles assert that EDx testing has a low yield in suspected DSP and is only needed for atypical presentations (a minority). However, many peer-reviewed articles indicate that EDx frequently changes diagnosis and management, and leads to a better understanding of the underlying pathology, severity, and prognosis. Overall, EDx is appropriate for most patients with new signs and symptoms of DSP. Muscle Nerve 55: 301-304, 2017.

Inflammation in the pathogenesis of lyme neuroborreliosis.

Lyme neuroborreliosis, caused by the spirochete Borrelia burgdorferi, affects both peripheral and central nervous systems. We assessed a causal role for inflammation in Lyme neuroborreliosis pathogenesis by evaluating the induced inflammatory changes in the central nervous system, spinal nerves, and dorsal root ganglia (DRG) of rhesus macaques that were inoculated intrathecally with live B. burgdorferi and either treated with dexamethasone or meloxicam (anti-inflammatory drugs) or left untreated. ELISA of cerebrospinal fluid showed significantly elevated levels of IL-6, IL-8, chemokine ligand 2, and CXCL13 and pleocytosis in all infected animals, except dexamethasone-treated animals. Cerebrospinal fluid and central nervous system tissues of infected animals were culture positive for B. burgdorferi regardless of treatment. B. burgdorferi antigen was detected in the DRG and dorsal roots by immunofluorescence staining and confocal microscopy. Histopathology revealed leptomeningitis, vasculitis, and focal inflammation in the central nervous system; necrotizing focal myelitis in the cervical spinal cord; radiculitis; neuritis and demyelination in the spinal roots; and inflammation with neurodegeneration in the DRG that was concomitant with significant neuronal and satellite glial cell apoptosis. These changes were absent in the dexamethasone-treated animals. Electromyography revealed persistent abnormalities in F-wave chronodispersion in nerve roots of a few infected animals; which were absent in dexamethasone-treated animals. These results suggest that inflammation has a causal role in the pathogenesis of acute Lyme neuroborreliosis.

The Lyme disease spirochete Borrelia burgdorferi induces inflammation and apoptosis in cells from dorsal root ganglia.

BACKGROUND: Lyme neuroborreliosis (LNB), caused by the spirochete Borrelia burgdorferi, affects both the peripheral and the central nervous systems. Radiculitis or nerve root inflammation, which can cause pain, sensory loss, and weakness, is the most common manifestation of peripheral LNB in humans. We previously reported that rhesus monkeys infected with B. burgdorferi develop radiculitis as well as inflammation in the dorsal root ganglia (DRG), with elevated levels of neuronal and satellite glial cell apoptosis in the DRG. We hypothesized that B. burgdorferi induces inflammatory mediators in glial and neuronal cells and that this inflammatory milieu precipitates glial and neuronal apoptosis. METHODS: To model peripheral neuropathy in LNB we incubated normal rhesus DRG tissue explants with live B. burgdorferi ex vivo and identified immune mediators, producer cells, and verified the presence of B. burgdorferi in tissue sections by immunofluorescence staining and confocal microscopy. We also set up primary cultures of DRG cells from normal adult rhesus macaques and incubated the cultures with live B. burgdorferi. Culture supernatants were subjected to multiplex ELISA to detect immune mediators, while the cells were evaluated for apoptosis by the in situ TUNEL assay. A role for inflammation in mediating apoptosis was assessed by evaluating the above phenomena in the presence and absence of various concentrations of the anti-inflammatory drug dexamethasone. As Schwann cells ensheath the dorsal roots of the DRG, we evaluated the potential of live B. burgdorferi to induce inflammatory mediators in human Schwann cell (HSC) cultures. RESULTS: Rhesus DRG tissue explants exposed to live B. burgdorferi showed localization of CCL2 and IL-6 in sensory neurons, satellite glial cells and Schwann cells while IL-8 was seen in satellite glial cells and Schwann cells. Live B. burgdorferi induced elevated levels of IL-6, IL-8 and CCL2 in HSC and DRG cultures and apoptosis of sensory neurons. Dexamethasone reduced the levels of immune mediators and neuronal apoptosis in a dose dependent manner. CONCLUSION: In this model, B. burgdorferi induced an inflammatory response and neuronal apoptosis of DRG. These pathophysiological processes could contribute to peripheral neuropathy in LNB.

Evidence-based guideline: treatment of painful diabetic neuropathy--report of the American Association of Neuromuscular and Electrodiagnostic Medicine, the American Academy of Neurology, and the American Academy of Physical Medicine & Rehabilitation.

The objective of this report was to develop a scientifically sound and clinically relevant evidence-based guideline for the treatment of painful diabetic neuropathy (PDN). The basic question that was asked was: "What is the efficacy of a given treatment (pharmacological: anticonvulsants, antidepressants, opioids, others; non-pharmacological: electrical stimulation, magnetic field treatment, low-intensity laser treatment, Reiki massage, others) to reduce pain and improve physical function and quality of life (QOL) in patients with PDN?" A systematic review of literature from 1960 to August 2008 was performed, and studies were classified according to the American Academy of Neurology classification of evidence scheme for a therapeutic article. Recommendations were linked to the strength of the evidence. The results indicate that pregabalin is established as effective and should be offered for relief of PDN (Level A). Venlafaxine, duloxetine, amitriptyline, gabapentin, valproate, opioids (morphine sulfate, tramadol, and oxycodone controlled-release), and capsaicin are probably effective and should be considered for treatment of PDN (Level B). Other treatments have less robust evidence, or the evidence is negative. Effective treatments for PDN are available, but many have side effects that limit their usefulness. Few studies have sufficient information on their effects on function and QOL.

Chikungunya encephalitis, a case series from an endemic country.

BACKGROUND: The Chikungunya Virus (CHIKV) was introduced into Honduras in 2015. Since then the WHO has reported more than 14,000 suspected cases in the country. OBJECTIVE: To describe the clinical, laboratory, neuroimaging, and pathological features of CHIKV encephalitis. PATIENTS AND METHODS: We evaluated all consecutive cases of CHIKV infection meeting encephalitis criteria at Hospital Escuela Universitario at Tegucigalpa, Honduras, during 2015. Who case definition was used: patient with neurological manifestations meeting clinical criteria (fever >38.5 °C, joint pain); resident/visitor in the last 15 days to an endemic area; laboratory confirmation with IgM/ELISA. Other etiologies were excluded by ancillary studies. RESULTS: Out of 95 cases with suspected CHIKV infection, 7 (7%) cases with CHIKV encephalitis were identified; mean age was 56 years and four were men. The mean latency from onset of symptoms to diagnosis was 5 five days. Clinical manifestations were: fever/arthralgia, headache/alteration of consciousness and status epilepticus. The EEG demonstrated slow background activity and generalized epileptiform discharges in three patients. Brain MRI showed bilateral white matter hyperintensities and one with focal encephalitis; CSF analysis demonstrated lymphocytic pleocytosis and hyperproteinorrachia. Two patients died. Postmortem brain examination of one patient revealed lymphocytic infiltrates with focal necrosis in hippocampus, frontal lobes and medulla oblongata. CONCLUSIONS: Neurological complications of CHIKV are infrequent, but may be severe. In this case series, the neurological manifestation was encephalitis. Predominant symptoms and signs were fever, behavioral abnormalities, headache and seizures. Because of the potential morbidity and mortality of CHIKV encephalitis, these patients should be admitted to hospital urgently.

Characterization of adult patients with Guillain-Barré syndrome during the arboviral infection outbreaks in Honduras.

Arbovirus infections have been associated with a wide spectrum of neurological manifestations. Among these, Guillain-Barré syndrome (GBS) is one of the most common. This study describes the characteristics of GBS associated with arbovirus infections during the outbreak which occurred in Honduras from January 2016 to February 2019. This was an observational retrospective study of adult patients who were diagnosed with GBS during that time. The diagnosis of GBS was based upon the criteria first published by Asbury, et al. and subsequently revised as the Brighton Criteria. A total of 91 patients with GBS constituted the study population. RT-PCR tests for ZIKV, CHIKV, and DENV arboviruses were performed in 47 (52%) of the patients. Of the tested population, 8/47 were positive for one of the arboviruses (5/8 for ZIKV, 3/8 for CHIKV; 0/8 for DENV). The clinical profile of the eight cases with GBS and arboviral infection did not differ significantly from the GBS patients who tested negative for ZIKV and CHIKV. In the cases with GBS and ZIKV, a parainfectious onset of the disease was suggested. Although not a strikingly large number of patients with GBS and arbovirus infection were seen, the close temporal relationship in these eight cases suggests an arbovirus (ZIKV and CHIKV) etiology.

Signs and symptoms versus nerve conduction studies to diagnose diabetic sensorimotor polyneuropathy: Cl vs. NPhys trial.

The purpose was to test whether physicians can validly and reproducibly diagnose diabetic sensorimotor polyneuropathy (DSPN). Twelve physicians assessed 24 patients with diabetes mellitus (DM) on consecutive days (576 examinations) with physical features and voice disguised. Results were compared to gold standard 75% group diagnosis (dx) and a nerve conduction score (Sigma5 NC nds). Masking of patients was achieved. Reproducibility measured by the kappa coefficient and compared to Sigma5 NC nd varied considerably among physicians: median and ranges: signs 0.8 (0.32-1.0); symptoms 0.79 (0.36-1.0), and diagnoses 0.47 (0.33-0.84), both low and high scores indicating poor performance. There was substantial agreement between 75% group dx and confirmed NC abnormality (abn). As compared to Sigma5 NC, individual physicians' clinical dx was excessively variable and frequently inaccurate. Study physician dx from signs and symptoms were excessively variable, often overestimating DSPN. Specific approaches to improving clinical proficiency should be tested.

Benzodiazepine Withdrawal Catatonia, Delirium, and Seizures in a Patient With Schizoaffective Disorder.

Benzodiazepine withdrawal symptoms vary from mild anxiety to life-threatening delirium or seizures. In susceptible individuals, such as those with mood disorders, benzodiazepine withdrawal may also precipitate catatonia. A 26-year-old man with schizoaffective disorder (depressed type with catatonia) ran out of lorazepam and presented with catatonia, delirium, and seizures. He was taking olanzapine, venlafaxine, and trazodone for schizoaffective disorder. Lorazepam 2 mg twice daily kept him free of catatonia for 6 months. Besides catatonia and delirium, lorazepam withdrawal also triggered convulsive seizures and nonconvulsive status epilepticus. He was admitted to the intensive care unit where he underwent continuous video-EEG monitoring. Catatonia resolved with lorazepam on day 2. Seizures stopped with levetiracetam, lacosamide, and propofol on day 4. His mental status was normal when he was discharged on day 6. If not immediately recognized and treated, catatonia and delirium can lead to significant morbidity or mortality. Unfortunately, physicians tend to overlook catatonia and delirium, especially if both syndromes are present. At first, we suspected that our patient had ictal catatonia, but video-EEG showed no clear-cut correlation between catatonia, seizures, and epileptiform activity. As with prior observations, the patient's catatonia was more sensitive to benzodiazepine withdrawal and treatment than his seizures. The efficacy of benzodiazepines in aborting catatonia, seizures, and mixed delirium-catatonia syndromes suggests a key pathogenetic role of abnormal GABA neurotransmission in these brain disorders.

Current practice patterns in CIDP: A cross-sectional survey of neurologists in the United States.

To evaluate how neurologists make decisions regarding chronic inflammatory demyelinating polyneuropathy (CIDP), we conducted a cross-sectional quantitative survey of 100 community neurologists in the United States. Only 13% cited using the European Federation of Neurological Societies/Peripheral Nerve Society guideline. In addition, variability in treatment approaches existed regarding the dose of IVIg used, the length of IVIg therapy before determining response, the outcome measures used to determine IVIg response, and the protocol for weaning off therapy. Forty-three percent reported giving doses that were lower than the recommended IVIg loading dose for CIDP. Many reported giving nonspecific patient education about the rationale of IVIg use and treatment duration. The finding that approximately half of community neurologists endorsed electrodiagnostic criteria that do not support CIDP diagnosis indicated difficulties relying heavily upon neurophysiologic studies in diagnostic guidelines. More education on CIDP diagnosis and treatment and a clear, actionable, clinically focused guideline would enhance best practices, particularly in the midst of high information flow and multiple guidelines.

SPS: Understanding the complexity.

INTRODUCTION: Stiff-person syndrome (SPS), first described in 1956 by Moersch and Woltman, is a progressive autoimmune disorder with core features of chronic fluctuating progressive truncal and limb rigidity and painful muscle spasms leading to gait difficulties, falls and an appearance that resembles tin soldiers. The syndrome is a rare, highly disabling disorder of the central nervous and frequently results in significant disability. Understanding of the etiology, clinical spectrum, diagnostic workup and therapeutic modalities for this painful and disabling disorder has vastly evolved over the past few years with more confidence in classifying and treating the patients. The purpose of this review is to increase the awareness, early detection, and treatment of this disabling disease. METHOD: PubMed was searched, all date inclusive, using the following phrases: stiff person syndrome,anti-Glutamic acid decarboxylase (Anti-GAD) antibody syndrome, Progressive encephalomyelitis with rigidity and myoclonus (PERM), and Paraneoplastic Stiff Person syndrome. No filters or restrictions were used. A total of 888 articles were identified. RESULTS: The results were narrowed to 190 citations after excluding non-English and duplicate reports. Clinical presentation, laboratory testing, treatment, and prognosis were categorized and summarized. DISCUSSION: In this article we will discuss the epidemiology, presentation and classification. Explain the pathophysiology of SPS and the autoimmune mechanisms involved. Discuss the diagnostic approach and treatments available, as well as, the prognosis and outcome.

Spatial distribution of Zika in Honduras during 2016-2017 using geographic information systems (GIS) - Implications for public health and travel medicine.

BACKGROUND: Zika virus (ZIKV) infection has significantly affected Latin America in 2015-2017. Most studies have been reported from Brazil and Colombia, and only a few from Central America. For these reasons, we analyzed the incidence, incidence rates and evolution of cases in Honduras from 2016 to 2017. METHODS: Using epidemiological weeks (EW) surveillance data on the ZIKV epidemics in Honduras, we estimated incidence rates (cases/100,000 population), and developed maps at national, departmental and municipal levels. RESULTS: From 1 January 2016 to 31 December 2017, a total of 32,607 cases of ZIKV were reported (98.5% in 2016 for an incidence rate of 36.85 cases/100,000 pop; 1% confirmed by RT-PCR). The highest peak was reached on the EW 6°, 2016 (2559 cases; 29.34 cases/100,000 pop). The department with the highest number of cases and incidence rate was Cortés (13,128 cases, 791.08 cases/100,000 pop in 2016). DISCUSSION: The pattern and evolution of ZIKV infection in Honduras have been similar to that which occurred for chikungunya in 2015. As previously reported, infection with chikungunya involved predominantly the central and capital area of the country, reaching incidences there >750 cases/100,000 pop. Studies using geographical information systems linked with clinical disease characteristics are necessary to attain accurate epidemiological data for public health systems. Such information is also useful for assessment of risk for travelers who visit specific areas in a destination country.

Electrodiagnostic criteria for diagnosis of ALS.

A consensus meeting was held to determine the best use and interpretation of electrophysiological data in the diagnosis of ALS. The utility of needle EMG and nerve conduction studies was affirmed. It is recommended that electrophysiological evidence for chronic neurogenic change should be taken as equivalent to clinical information in the recognition of involvement of individual muscles in a limb. In addition, in the context of a suspected clinical diagnosis of ALS, fasciculation potentials should be taken as equivalent to fibrillation potentials and positive sharp waves in recognising denervation. The importance of searching for instability in fasciculation potentials and in motor unit potentials in ALS is stressed. These changes in the interpretation of electrophysiological data render obsolete the category Probable Laboratory-Supported ALS in the modified El Escorial diagnostic criteria for ALS. Methods for detection of upper motor neuron abnormality appear sensitive but require further study, particularly regarding their value when clinical signs of upper motor neuron lesion are uncertain.

Whipple's disease.

Whipple's disease is a rare, chronic, systemic infectious disorder with prominent intestinal manifestations. It presents with weight loss, arthralgia, diarrhea, and abdominal pain. There are different entities of infection or carriage, respectively, classical Whipple's disease, localized WD, and Isolated Neurological WD. The disease is commonly diagnosed by biopsy of lymph node or small-bowel. Histological detection within duodenal biopsies with "Periodic acid Schiff" (PAS) staining still is first choice for the diagnosis of classical Whipple's disease. PCR or immunohistochemistry can identify the agent more specifically, and DNA sequencing for Tropheryma whipplei on lymphocytes from blood and cerebrospinal fluid from PCR-positive specimens, is essential. Cell-mediated immunity in active and inactive Whipple's disease has subtle defects that might predispose some individuals to symptomatic infection with this bacillus. Successful treatment can be achieved in most of the cases by antimicrobial therapy. WD can be progressive lethal. Immune reconstitution inflammatory syndrome (IRIS) might complicate the course of treatment and in worst case end fatal.

Statin-associated myopathy with normal creatine kinase levels.

BACKGROUND: Muscle symptoms in patients who are treated with statins and have normal creatine kinase levels are not well understood. OBJECTIVE: To report biopsy-confirmed myopathy and normal creatine kinase levels associated with statin use. DESIGN: Case reports from preliminary analysis of an ongoing clinical trial. SETTING: Clinical research center in a community hospital. PATIENTS: Four patients with muscle symptoms that developed during statin therapy and reversed during placebo use. MEASUREMENTS: 1) Patients' ability to identify blinded statin therapy and 2) standard measures of functional capacity and muscle strength. RESULTS: All four patients repeatedly distinguished blinded statin therapy from placebo. Strength testing confirmed weakness during statin therapy that reversed during placebo use. Muscle biopsies showed evidence of mitochondrial dysfunction, including abnormally increased lipid stores, fibers that did not stain for cytochrome oxidase activity, and ragged red fibers. These findings reversed in the three patients who had repeated biopsy when they were not receiving statins. Creatine kinase levels were normal in all four patients despite the presence of significant myopathy. CONCLUSION: Some patients who develop muscle symptoms while receiving statin therapy have demonstrable weakness and histopathologic findings of myopathy despite normal serum creatine kinase levels.