Treatment response in patients with clinical and supportive laboratory features of chronic inflammatory demyelinating polyneuropathy without demyelinative findings on nerve conduction studies: A retrospective study.

INTRODUCTION/AIMS: Not all patients with chronic inflammatory demyelinating polyneuropathy (CIDP) have evidence of demyelination on nerve conduction studies (NCS). Patients with "supportive" evidence of CIDP on cerebrospinal fluid (CSF), magnetic resonance imaging (MRI), ultrasound (US), or nerve biopsy but not on NCS, often receive immunomodulating therapy. We evaluated the treatment response of patients with clinical and supportive features of CIDP lacking NCS evidence of demyelination. METHODS: Retrospective chart review was conducted on 232 patients who met CIDP clinical criteria and were treated with disease-modifying therapy. Patients included did not have NCS criteria of demyelination, but did have supportive CSF, MRI, or US findings consistent with CIDP. A positive treatment response was defined as at least a one-point improvement in the modified Rankin scale (mRS), or a four-point increase in the Medical Research Council sum score (MRCSS). RESULTS: Twenty patients met criteria: 17 of the 18 (94%) patients with CSF protein >45 mg/dL, 6 of the 14 (43%) with MRI lumbosacral root or plexus enhancement, and 4 of the 6 (67%) with enlarged proximal nerves on US. Eighteen patients received intravenous immunoglobulin, 10 corticosteroids, one plasma exchange, and six other immunomodulatory therapies. Twelve patients had a positive treatment response on the MRCSS or mRS. The presence of MRI lumbosacral root or plexus enhancement was associated with a positive treatment response. DISCUSSION: A trial of immunomodulating treatment should be considered for patients with clinical features of CIDP in the absence of NCS evidence of demyelination, particularly when there is MRI lumbosacral root or plexus enhancement.

Diagnosis of Ulnar Neuropathy at the Elbow Using Ultrasound - A Comparison to Electrophysiologic Studies.

PURPOSE: Given the relatively high false negative rate of electrodiagnostic studies (EDX) in patients with clinically diagnosed ulnar neuropathy at the elbow (UNE), we sought to determine whether an alternative objective test could more effectively detect UNE. Additionally, we proposed to determine the relationship between the cross-sectional area (CSA) of the ulnar nerve on ultrasound (US), EDX, and clinical symptoms. METHODS: This was a retrospective study of patients presenting with symptomatic UNE. The performance characteristics of EDX versus ultrasound were calculated using the clinical diagnosis of UNE as the reference standard. Standard EDX studies and US of the ulnar nerve were analyzed. Maximal CSA of the ulnar nerve and EDX severity were analyzed for patients with each combination of US-positive/negative and EDX-positive/negative findings. RESULTS: Analysis was performed on 89 patients and 115 nerves with signs and symptoms of cubital tunnel syndrome. In total, 56 (49%) nerves were diagnosed as mild UNE, 32 (28%) nerves were diagnosed as moderate UNE, 17 (15%) nerves were diagnosed as severe UNE, and 10 (8%) nerves were negative for UNE by EDX. Maximal-maximal CSA was highly correlated with disease severity as determined by nerve conduction studies/electromyography. Compared with EDX+/US+, patients with EDX-/US+ showed higher rates of ulnar sensory loss and elbow tenderness with similar rates of positive Tinel and intrinsic muscle atrophy. In this sample of patients with clinically diagnosed UNE, 91.3% of the patients demonstrated positive EDX studies, whereas 94.8% had a positive US. CONCLUSIONS: Ultrasound is an alternative to EDX that could be incorporated clinically in the diagnosis and management of UNE. Ultrasound was able to consistently detect clinically positive cubital tunnel syndrome demonstrating its utility as a confirmatory or supplemental test to the clinical assessment if one is required. Ultrasound additionally may be able to better identify patients with early stages of UNE with negative EDX findings. TYPE OF STUDY/LEVEL OF EVIDENCE: Diagnostic IV.

A systematic review of the potential consequences of abnormal serum levels of vitamin B6 in people living with Parkinson's disease.

The prevalences of polyneuropathy and epilepsy are higher in people living with Parkinson's disease (PwPD) when compared to older adults. Vitamin B6 is widely available and affordable. PwPD are at higher risk of having abnormal serum levels of vitamin B6, which are associated with polyneuropathy and epilepsy that are potentially preventable and treatable. Potential contributors to abnormal B6 levels in PwPD include age, dietary habits, vitamin supplement misuse, gastrointestinal dysfunction and complex interactions with levodopa. The literature on the potential consequences of abnormal B6 levels in PwPD is limited by a small number of observational studies focused on polyneuropathy and epilepsy. Abnormal B6 levels have been reported in 60 of 145 PwPD (41.4% relative frequency). Low B6 levels were reported in 52 PwPD and high B6 levels were reported in 8 PwPD. There were 14 PwPD, polyneuropathy and low B6. There were 4 PwPD, polyneuropathy and high B6. There were 4 PwPD, epilepsy and low B6. Vitamin B6 level was low in 44.6% of PwPD receiving levodopa-carbidopa intestinal gel and in 30.1% of PwPD receiving oral levodopa-carbidopa. In almost all studies reporting low B6 in PwPD receiving oral levodopa-carbidopa, the dose of levodopa was ≥1000 mg/day. Rigorous epidemiological studies will clarify the prevalence, natural history and clinical relevance of abnormal serum levels of vitamin B6 in PwPD. These studies should account for diet, vitamin supplement use, gastrointestinal dysfunction, concurrent levels of vitamin B12, folate, homocysteine and methylmalonic acid, formulations and dosages of levodopa and other medications commonly used in PwPD.

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.

Recovery of foot drop in chronic inflammatory demyelinating polyneuropathy (CIDP).

INTRODUCTION/AIMS: Foot drop is common in chronic inflammatory demyelinating polyneuropathy (CIDP), but its prognosis is uncertain. METHODS: CIDP patients with less than anti-gravity strength (<3/5 power) of ankle dorsiflexion (ADF) on Medical Research Council manual muscle testing on presentation at our center were identified by retrospective review. After initiation of standard treatment, ADF power was serially tabulated, and predictors of recovery were determined. RESULTS: Of the 27 identified patients, ADF power at presentation was <3/5 in 48/54 legs. At 1 y after treatment, ADF power improved to >/= 3/5 in 17/27 patients in one (N = 6) or both (N = 11) legs. On multi-variate analysis, predictors of recovery of ADF power were tibialis anterior compound muscle action potential amplitude at presentation, shorter disease duration, and female gender. DISCUSSION: Foot drop improves to anti-gravity power in most treated CIDP patients depending in part on the severity of fibular motor axon loss at onset of treatment.

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.

Myotonic dystrophy health index: Correlations with clinical tests and patient function.

INTRODUCTION: The Myotonic Dystrophy Health Index (MDHI) is a disease-specific patient-reported outcome measure. Here, we examine the associations between the MDHI and other measures of disease burden in a cohort of individuals with myotonic dystrophy type-1 (DM1). METHODS: We conducted a cross-sectional study of 70 patients with DM1. We examined the associations between MDHI total and subscale scores and scores from other clinical tests. Participants completed assessments of strength, myotonia, motor and respiratory function, ambulation, and body composition. Participants also provided blood samples, underwent physician evaluations, and completed other patient-reported outcome measures. RESULTS: MDHI total and subscale scores were strongly associated with muscle strength, myotonia, motor function, and other clinical measures. CONCLUSIONS: Patient-reported health status, as measured by the MDHI, is associated with alternative measures of clinical health. These results support the use of the MDHI as a valid tool to measure disease burden in DM1 patients.

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.