Long Exercise Test in Periodic Paralysis: A Bayesian Analysis.

INTRODUCTION: The long exercise test (LET) is used to assess the diagnosis of periodic paralysis (PP), but LET methodology and normal "cutoff" values vary. METHODS: To determine optimal LET methodology and cutoffs, we reviewed LET data (abductor digiti minimi motor response amplitude, area) from 55 patients with PP (32 genetically definite) and 125 controls. Receiver operating characteristic curves were constructed, and area under the curve (AUC) was calculated to compare (1) peak-to-nadir versus baseline-to-nadir methodologies and (2) amplitude versus area decrements. Using bayesian principles, we calculated optimal cutoff decrements that achieved 95% posttest probability of PP for various pretest probabilities (PreTPs). RESULTS: AUC was highest for peak-to-nadir methodology and equal for amplitude and area decrements. For PreTP ≤ 50%, optimal decrement cutoffs (peak-to-nadir) were > 40% (amplitude) or > 50% (area). DISCUSSION: For confirmation of PP, our data endorse the diagnostic utility of peak-to-nadir LET methodology using 40% amplitude or 50% area decrement cutoffs for PreTP ≤50%. Muscle Nerve 59:47-54, 2019.

Acute nutritional axonal neuropathy.

INTRODUCTION: This study describes clinical, laboratory, and electrodiagnostic features of a severe acute axonal polyneuropathy common to patients with acute nutritional deficiency in the setting of alcoholism, bariatric surgery (BS), or anorexia. METHODS: Retrospective analysis of clinical, electrodiagnostic, and laboratory data of patients with acute axonal neuropathy. RESULTS: Thirteen patients were identified with a severe, painful, sensory or sensorimotor axonal polyneuropathy that developed over 2-12 weeks with sensory ataxia, areflexia, variable muscle weakness, poor nutritional status, and weight loss, often with prolonged vomiting and normal cerebrospinal fluid protein. Vitamin B6 was low in half and thiamine was low in all patients when obtained before supplementation. Patients improved with weight gain and vitamin supplementation, with motor greater than sensory recovery. DISCUSSION: We suggest that acute or subacute axonal neuropathy in patients with weight loss or vomiting associated with alcohol abuse, BS, or dietary deficiency is one syndrome, caused by micronutrient deficiencies. Muscle Nerve 57: 33-39, 2018.

Diffuse age-related lumbar mri changes confound diagnosis of single (L5) root lesions.

INTRODUCTION: L5 radiculopathy has characteristic clinical and electrodiagnostic features including: radicular pain; weakness or denervation of hip abductors, ankle dorsiflexors, and inverters; and pre-ganglionic dorsal foot sensory loss. It is unknown how often patients with this distinctive clinical-electrodiagnostic presentation have isolated L5-root compression on neuroimaging or more widespread, possibly age-related, lumbar neuroforaminal or spinal stenosis. METHODS: A study-blinded neuroradiologist quantitated lumbosacral neuroforaminal, lateral recess, and spinal stenosis in 26 consecutive patients with unilateral, clinically and EMG-ascertained L5 monoradiculopathy, and quantitated a global neuroforaminal and spinal stenosis score (SSS). RESULTS: Only 9 patients (35%) had isolated L5-root compression, 14 (54%) had multi-root compression, and 3 (12%) had normal neuroimaging. Increasing age correlated with SSS, and the 9 patients with isolated L5-root compression were significantly younger than patients with multi-root involvement. CONCLUSIONS: This study underscores the role of clinical and electrodiagnostic data when interpreting lumbosacral neuroimaging, particularly in older patients.

Electrodiagnosis of ulnar neuropathy at the elbow (Une): a Bayesian approach.

INTRODUCTION: In ulnar neuropathy at the elbow (UNE), we determined how electrodiagnostic cutoffs [across-elbow ulnar motor conduction velocity slowing (AECV-slowing), drop in across-elbow vs. forearm CV (AECV-drop)] depend on pretest probability (PreTP). METHODS: Fifty clinically defined UNE patients and 50 controls underwent ulnar conduction testing recording abductor digiti minimi (ADM) and first dorsal interosseous (FDI), stimulating wrist, below-elbow, and 6-, 8-, and 10-cm more proximally. For various PreTPs of UNE, the cutoffs required to confirm UNE (defined as posttest probability = 95%) were determined with receiver operator characteristic (ROC) curves and Bayes Theorem. RESULTS: On ROC and Bayesian analyses, the ADM 10-cm montage was optimal. For PreTP = 0.25, the confirmatory cutoffs were >23 m/s (AECV-drop), and <38 m/s (AECV-slowing); for PreTP = 0.75, they were much less conservative: >14 m/s, and <47 m/s, respectively. CONCLUSIONS: (1) In UNE, electrodiagnostic cutoffs are critically dependent on PreTP; rigid cutoffs are problematic. (2) AE distances should be standardized and at least 10 cm.

Visualization of the diaphragm muscle with ultrasound improves diagnostic accuracy of phrenic nerve conduction studies.

INTRODUCTION: Evaluation of phrenic neuropathy (PN) with phrenic nerve conduction studies (PNCS) is associated with false negatives. Visualization of diaphragmatic muscle twitch with diaphragm ultrasound (DUS) when performing PNCS may help to solve this problem. METHODS: We performed bilateral, simultaneous DUS-PNCS in 10 healthy adults and 12 patients with PN. The amplitude of the diaphragm compound muscle action potential (CMAP) (on PNCS) and twitch (on DUS) was calculated. RESULTS: Control subjects had <38% side-to-side asymmetry in twitch amplitude (on DUS) and 53% asymmetry in phrenic CMAP (on PCNS). In the 12 patients with PN, 12 phrenic neuropathies were detected. Three of these patients had either significant side-to-side asymmetry or absolute reduction in diaphragm movement that was not detected with PNCS. There were no cases in which the PNCS showed an abnormality but the DUS did not. CONCLUSIONS: The addition of DUS to PNCS enhances diagnostic accuracy in PN.

The diagnosis and treatment of myotonic disorders.

Myotonia is a defining clinical symptom and sign common to a relatively small group of muscle diseases, including the myotonic dystrophies and the nondystrophic myotonic disorders. Myotonia can be observed on clinical examination, as can its electrical correlate, myotonic discharges, on electrodiagnostic testing. Research interest in the myotonic disorders continues to expand rapidly, which justifies a review of the scientific bases, clinical manifestations, and numerous therapeutic approaches associated with these disorders. We review the pathomechanisms of myotonia, the clinical features of the dystrophic and nondystrophic myotonic disorders, and the diagnostic approach and treatment options for patients with symptomatic myotonia.

Clinical Spectrum and Prognosis in Patients With Acute Nutritional Axonal Neuropathy.

BACKGROUND AND OBJECTIVES: To describe the clinical, micronutrient, and electrophysiologic spectra and prognosis in patients with acute nutritional axonal neuropathy (ANAN). METHODS: Patients with ANAN were identified between 1999 and 2020 by a retrospective review of our EMG database and electronic health records and categorized on clinical and electrodiagnostic grounds, as pure sensory, sensorimotor, or pure motor; and by risk factor (alcohol use disorder, bariatric surgery, or anorexia). Laboratory abnormalities were recorded including thiamine, vitamin B6, B12, and E, folate, and copper. Ambulatory and neuropathic pain status at last follow-up were recorded. RESULTS: Of 40 patients with ANAN, 21 had alcohol use disorder, 10 were anorexic, and 9 had recently undergone bariatric surgery. Their neuropathy was pure sensory in 14 (7 with low thiamine), sensorimotor in 23 (8 with low thiamine), and pure motor in 3 (1 with low thiamine). Vitamin B1 was most commonly low (85%), followed by vitamin B6 (77%) and folate (50%). The risk factor and neuropathy type were not associated with a particular micronutrient deficiency. Of the 37 patients who were seen in follow-up, only 13 (35%) were walking independently, and only 8 (22%) were pain free at the last follow-up visit at a mean of 22 months (range 2-88 months) from onset. DISCUSSION: The spectrum of ANAN is wide, ranging from: (1) a pure sensory neuropathy with areflexia, limb and gait ataxia, neuropathic pain, and unevocable sensory responses to (2) a motor axonal neuropathy with low-amplitude motor responses without conduction slowing, block, or dispersion, and (3) a mixed sensorimotor axonal polyneuropathy. Specific micronutrient deficiencies or risk factors do not predict neuropathy subtype. The subgroup of patients with ANAN with documented thiamine deficiency also range from pure sensory to pure motor, and only a minority have Wernicke encephalopathy. We do not know whether coexistent micronutrient deficiencies may help explain the wide clinical spectrum of thiamine-deficient ANAN. The prognosis of ANAN is guarded due to residual neuropathic pain and slow recovery of independent ambulation. Therefore, early recognition of patients at risk is important.

Unexpected neuroimaging abnormalities in patients with apparent C8 radiculopathy: broadening the clinical spectrum.

INTRODUCTION: C8-root impingement by C7/T1 lesions on neuroimaging studies is not consistently observed in C8 radiculopathy. We hypothesized that C7 or T1 root lesions (with a pre- or postfixed plexus) or cervical myelopathy might explain some "C8 radiculopathies" without C8 root compression. METHODS: Retrospective analysis of cervical neuroimaging in 31 consecutive patients with EMG-confirmed C8 radiculopathy. RESULTS: Five patients (16%) had C8-root compression at C7/T1. Of those without C8-root compression, 5 (16%) had C7-root compression at C6/7, one (3%) had T1-root compression at T1/T2, 7 (23%) had cervical cord compression at or above the C6/7 level, 4 (13%) had intramedullary cervical lesions, and 9 (29%) had mild or nonspecific findings. CONCLUSIONS: C8 radiculopathy without C8-root compression may be due to C7-root compression in the setting of a "prefixed" brachial plexus, upper cervical cord compression with vascular compromise of the distal cervical spinal cord ("myelopathic hand"), or intramedullary cervical cord lesions.

Neurological manifestations of primary Sjogren's syndrome.

PURPOSE OF REVIEW: This review summarizes our current understanding of the neurological manifestations of primary Sjogren's syndrome (PSS), their pathophysiology, and treatment. RECENT FINDINGS: Prevalence of neurological manifestations in PSS varies widely from 10 to 60%, with pure or predominantly sensory polyneuropathies as the most common neurologic manifestation (e.g. sensory ataxic or small fiber sensory painful neuropathy). Mononeuropathy multiplex, polyradiculopathy, symptomatic dysautonomia, cranial neuropathy, myopathy, and central nervous system involvement are less common. PSS-associated sensory neuropathy is often the presenting feature of Sjogren's syndrome and, therefore, a high index of suspicion is required, particularly in female patients with nonlength-dependent, painful, or ataxic sensory neuropathies or those with trigeminal sensory and autonomic involvement. The pathophysiological basis of PSS-associated neuropathy is still unclear. Dorsal root ganglionitis and peripheral nerve vasculitis have been observed on histological examination of biopsy and autopsy samples. A few studies have explored the fundamental role of humoral autoimmune mechanisms. Small, uncontrolled, treatment trials with numerous immunomodulatory agents have reported variable benefit in PSS-associated neuropathy, particularly corticosteroids for mononeuritis multiplex and intravenous immunoglobulin for small fiber or sensory ataxic neuropathy. SUMMARY: The clinical and histological spectrum of neurological manifestations of Sjogren's syndrome is becoming clear. The field needs further exploration of basic neuroimmunological mechanisms of neural injury, and controlled treatment trials.

Evoked myotonia can be "dialed-up" by increasing stimulus train length in myotonic dystrophy type 1.

It is unknown how evoked myotonia varies with stimulus frequency or train length, or how it compares to voluntary myotonia in myotonic dystrophy type 1 (DM1). First dorsal interosseous (FDI) tetanic contractions evoked by trains of 10-20 ulnar nerve stimuli at 10-50 HZ were recorded in 10 DM1 patients and 10 normals. For comparison, maximum voluntary handgrip contractions were also recorded. An automated computer program placed cursors along the declining (relaxation) phase of the force recordings at 90% and 5% of peak force (PF) and calculated relaxation times (RTs) between these points. For all stimulus frequencies and train lengths, evoked RTs were much shorter, and evoked PFs were much greater in normals than in DM1. In normals, evoked RT was independent of stimulus frequency and train length, while in DM1 RT was longer for train lengths of 20 stimuli (mean: 9 s in DM1; 0.20 in normals) than for 10 stimuli (mean: 3 s in DM1, 0.19 in normals), but it did not change with stimulus frequency. In both groups PF increased greatly as stimulus frequency rose from 10-50 HZ but only slightly as train length rose from 10-20 stimuli. Voluntary handgrip RT (mean: 1.9 s) was less than evoked FDI RT (mean: 9 s). In DM1, evoked RT can be "dialed up" by increasing stimulus train length. Evoked myotonia testing utilizing a stimulus paradigm of at least 20 stimuli at 30-50 HZ may be useful in antimyotonic drug trials, particularly when grip RT is normal or equivocal.

Yield of the sural/radial ratio versus the medial plantar nerve in sensory neuropathies with a normal sural response.

The electrodiagnostic yield of the medial plantar nerve action potential (NAP) amplitude versus the sural/radial amplitude ratio (SRAR) was determined in 110 consecutive patients with clinically diagnosed distal sensory polyneuropathy (SN) and normal sural responses. Forty-five consecutive patients with clinically diagnosed lumbosacral radiculopathy served as disease controls. Of the 110 SN patients, 32 were classified clinically as SN with large-fiber involvement (SN-LFI), whereas 78 had clinically pure small-fiber SN. Plantar NAP amplitudes were abnormal in 18 of 32 patients (56%) with SN-LFI, and 15 of 78 (19%) with small-fiber SN. A SRAR <0.21 (fifth percentile of normal) was found in 7 of 32 patients (22%) with SN-LFI and 8 of 78 (10%) with small-fiber SN. In the control group, the medial plantar NAP was normal in all 45 subjects (100%), whereas the SRAR was >0.21 in 43 subjects (96%). Thus, for a 50% pretest probability of SN-LFI, the positive predictive value of an abnormal medial plantar was 100% versus 85% for a SRAR <0.21. The medial plantar NAP amplitude is a more useful measure of SN, than is the SRAR, in patients under age 70, with suspected SN-LFI. The yield of the SRAR and plantar NAP amplitude is poor when clinical signs of large-fiber sensory dysfunction are lacking.

Pediatric CIDP: Clinical Features and Response to Treatment.

OBJECTIVES: Childhood chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) responds favorably to immunomodulatory treatment. However, the optimal sequencing and selection of immunotherapy is uncertain. METHODS: Using accepted diagnostic criteria, pediatric patients with CIDP seen at our center from 1999 to 2015 were identified retrospectively through medical record review. Clinical details and treatment responses were tabulated. RESULTS: Ten patients (age 4-16, 6 women) with definite (N = 8) or possible (N = 2) CIDP met criteria. All were initially treated with IVIg; 6 responded but 4 did not. All 4 IVIG nonresponders improved with twice-weekly high-dose oral prednisone, as did 1 IVIg responder who was also treated with twice-weekly oral prednisone when IVIg was discontinued. Pulse steroids were well tolerated. CONCLUSIONS: Pulse oral corticosteroid therapy holds promise as an alternative treatment to IVIG in pediatric CIDP. Future multicenter studies are warranted to determine the comparative efficacy and safety of weekly pulse oral corticosteroids versus IVIg in pediatric CIDP.

Electrophysiologic features of SYT2 mutations causing a treatable neuromuscular syndrome.

OBJECTIVES: To describe the clinical and electrophysiologic features of synaptotagmin II (SYT2) mutations, a novel neuromuscular syndrome characterized by foot deformities and fatigable ocular and lower limb weakness, and the response to modulators of acetylcholine release. METHODS: We performed detailed clinical and neurophysiologic assessment in 2 multigenerational families with dominant SYT2 mutations (c.920T>G [p.Asp307Ala] and c.923G>A [p.Pro308Leu]). Serial clinical and electrophysiologic assessments were performed in members of one family treated first with pyridostigmine and then with 3,4-diaminopyridine. RESULTS: Electrophysiologic testing revealed features indicative of a presynaptic deficit in neurotransmitter release with posttetanic potentiation lasting up to 60 minutes. Treatment with 3,4-diaminopyridine produced both a clinical benefit and an improvement in neuromuscular transmission. CONCLUSION: SYT2 mutations cause a novel and potentially treatable complex presynaptic congenital myasthenic syndrome characterized by motor neuropathy causing lower limb wasting and foot deformities, with reflex potentiation following exercise and a uniquely prolonged period of posttetanic potentiation.

Dispersion of the distal compound muscle action potential as a diagnostic criterion for chronic inflammatory demyelinating polyneuropathy.

OBJECTIVE: To assess distal compound muscle action potential (DCMAP) duration as a diagnostic criterion for chronic inflammatory demyelinating polyneuropathy (CIDP). BACKGROUND: Current electrodiagnostic criteria for CIDP have high specificity but limited sensitivity. Prolonged DCMAP duration has been reported in acute inflammatory demyelinating polyneuropathy. The authors have compared DCMAP duration in patients with CIDP, diabetic polyneuropathy (DP), ALS, and musculoskeletal pain syndrome (MSP) to determine whether it enhances the sensitivity of electrodiagnostic criteria for CIDP. METHODS: Data from 23 CIDP, 34 DP, 34 ALS, and 54 MSP patients were reviewed. The time interval between onset of the first negative peak and return to baseline of the last negative peak of the DCMAP was calculated for each nerve. To distinguish CIDP from DP, ALS, and MSP, optimal cutoff values for DCMAP duration were achieved with receiver-operating characteristic curves. The sensitivity and specificity of these cutoff values were compared with each of four sets of electrodiagnostic criteria for CIDP. RESULTS: Mean DCMAP duration in CIDP was significantly longer than in DP, ALS, and MSP. The sensitivity of existing electrodiagnostic criteria for CIDP ranged between 0.43 and 0.61. Their specificity vs DP or ALS was 0.91 to 1. Using DCMAP duration of >/=9 milliseconds for any of four motor nerves yielded a sensitivity of 0.78 for CIDP and specificity of 0.94 vs DP or ALS. Adding DCMAP duration criteria to any one of the three accepted criteria enhanced their sensitivity with little sacrifice of specificity. CONCLUSION: Quantitation of DCMAP dispersion shows promise as a sensitive and specific adjunctive electrodiagnostic criterion for CIDP.

Electrodiagnosis of ulnar neuropathy at the wrist: conduction block versus traditional tests.

BACKGROUND: Compared to ulnar neuropathy at the elbow (UNE), ulnar neuropathy at the wrist (UNW) is rarer and more difficult to localize with routine electrophysiologic studies. METHODS: By stimulating the ulnar nerve at the wrist and palm, and recording from first dorsal interosseous (FDI), the sensitivity and specificity of conduction block (CB) and slow conduction velocity (CV) of FDI fibers across the wrist was compared to traditional electrodiagnostic techniques for localization of UNW. Twenty patients with clinically defined UNW (due mainly to wrist trauma), 30 normal controls, and 20 disease controls with severe (n = 10) and mild (n = 10) UNE were evaluated prospectively. The upper (mean +2.5 SD) and lower (mean -2.5 SD) limits for all measurements were derived from the normal controls. RESULTS: The UNW patients showed: slow wrist-palm FDI CV (<37 m/s) in 16 (80%); definite or probable CB in 14 (70%); prolonged distal latency (DL) to FDI (>4.5 milliseconds) in 12 (60%), to ulnar-innervated palmar interosseous (PI) versus median-innervated lumbrical (L) in 12 (60%), and to abductor digiti minimi (ADM) in 11 (55%). However, only CB and slow wrist-palm FDI CV (<37 m/s) were specific for UNW; prolonged DL to FDI was found in 4 patients (40%), to ADM in 4 patients (40%), and to PI in 1 patient (10%) with severe UNE. Overall, CB or slow wrist-palm FDI CV was present in 19 patients with UNW (95%). EMG failed to differentiate UNW from UNE, because forearm ulnar-innervated muscles were typically normal in UNW, but also often normal in mild UNE. CONCLUSIONS: In UNW, an additional palmar stimulation site improves electrodiagnostic yield, and demonstrates that CB is an important cause of muscle weakness.