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.

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.

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.

Infectious neuropathies.

PURPOSE OF REVIEW: Infections are important, potentially treatable causes of peripheral nervous system disease. This article reviews the clinical presentation and management of several common peripheral nervous system diseases due to viral, bacterial, spirochetal, and parasitic infections. RECENT FINDINGS: The clinical presentation and evaluation of infectious peripheral nervous system diseases are well established. Advances in the treatment and, in some cases, the prevention of these diseases are still evolving. SUMMARY: A diverse range of peripheral nervous system diseases, including peripheral neuropathy, radiculopathy, radiculomyelopathy, cranial neuropathy, and motor neuropathy, are caused by numerous infectious agents. In some patients, peripheral neuropathy may be a side effect of anti-infectious drugs. Infectious neuropathies are important to recognize as they are potentially treatable. This article discusses the clinical presentation, evaluation, and treatment of several common peripheral nervous system diseases caused by viral, bacterial, spirochetal, and parasitic infections, as well as some peripheral nerve disorders caused by adverse effects of the treatments of these infectious diseases.

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.

Electrodiagnosis of myotonic disorders.

Clinical and electrical myotonia is caused by a small group of neuromuscular disorders. This article reviews myotonia and its differential diagnosis. The use of electrodiagnostic testing to evaluate the primary myotonic disorders (myotonic dystrophy and the nondystrophic myotonias) is also discussed.

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.

Open-label trial of recombinant human insulin-like growth factor 1/recombinant human insulin-like growth factor binding protein 3 in myotonic dystrophy type 1.

OBJECTIVE: To evaluate the safety and tolerability of recombinant human insulin-like growth factor 1 (rhIGF-1) complexed with IGF binding protein 3 (rhIGF-1/rhIGFBP-3) in patients with myotonic dystrophy type 1 (DM1). DESIGN: Open-label dose-escalation clinical trial. SETTING: University medical center. PARTICIPANTS: Fifteen moderately affected ambulatory participants with genetically proven myotonic dystrophy type 1. INTERVENTION: Participants received escalating dosages of subcutaneous rhIGF-1/rhIGFBP-3 for 24 weeks followed by a 16-week washout period. MAIN OUTCOME MEASURES: Serial assessments of safety, muscle mass, muscle function, and metabolic state were performed. The primary outcome variable was the ability of participants to complete 24 weeks receiving rhIGF-1/ rhIGFBP-3 treatment. RESULTS: All participants tolerated rhIGF-1/rhIGFBP-3. There were no significant changes in muscle strength or functional outcomes measures. Lean body muscle mass measured by dual-energy x-ray absorptiometry increased by 1.95 kg (P < .001) after treatment. Participants also experienced a mean reduction in triglyceride levels of 47 mg/dL (P = .002), a mean increase in HDL levels of 5.0 mg/dL (P = .03), a mean reduction in hemoglobin A(1c) levels of 0.15% (P = .03), and a mean increase in testosterone level (in men) of 203 ng/dL (P = .002) while taking rhIGF-1/rhIGFBP-3. Mild reactions at the injection site occurred (9 participants), as did mild transient hypoglycemia (3), lightheadedness (2), and transient papilledema (1). CONCLUSIONS: Treatment with rhIGF-1/rhIGFBP-3 was generally well tolerated in patients with myotonic dystrophy type 1. Treatment with rhIGF-1/rhIGFBP-3 was associated with increased lean body mass and improvement in metabolism but not increased muscle strength or function. Larger randomized controlled trials would be needed to further evaluate the efficacy and safety of this medication in patients with neuromuscular disease. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00233519.

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.