Objective:
Occasionally, diabetic patients develop painless, lower‐limb, motor predominant neuropathy. Whether this is a variant of diabetic lumbosacral radiculoplexus neuropathy (DLRPN) (a painful ...disorder from ischemic injury and microvasculitis), a variant of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) or another disorder is unsettled. Here, we characterize the clinical and pathological features of painless diabetic motor predominant neuropathy.
Methods:
We identified patients with this syndrome who underwent nerve biopsy. We compared pathological features to 33 DLRPN and 25 CIDP biopsies.
Results:
23 patients were identified (22 had type 2 diabetes mellitus); 12 men; median age 62.2 years (range 36–78); median weight loss 30 pounds (range 0–100). Overall, the clinical features were similar to DLRPN except painless patients had more symmetrical and upper limb involvement, with slower progression and more severe impairment. Physiological testing demonstrated pan‐modality sensory loss, autonomic abnormalities and axonal polyradiculoneuropathies. Nerve biopsies were similar to DLPRN showing ischemic injury (multifocal fiber loss 11/23, perineural thickening 18/23, injury neuroma 11/23, neovascularization 17/23) and evidence of altered immunity and microvasculitis (epineurial perivascular inflammation 23/23, prior bleeding 11/23, vessel wall inflammation 15/23, and microvasculitis 3/23). In contrast, CIDP biopsies did not show ischemic injury or microvasculitis but revealed demyelination and onion‐bulbs.
Interpretation:
1) Painless diabetic motor neuropathy is painless DLRPN and not CIDP and is caused by ischemic injury and microvasculitis. 2) The clinical features of painless DLRPN are different from typical DLPRN being more insidious and symmetrical with slower evolution. 3) The slower evolution may explain the lack of pain. Ann Neurol 2010;
Article Note: Superficial radial nerve biopsy from a patient with focal sensory chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) showing a perivascular epineurial inflammatory ...collection (top panel, paraffin cross-section stained with LFB/PAS), and onion-bulb formation (evidence of ongoing demyelination and remyelination middle panel and at high magnification bottom panel). These pathological findings provide evidence of longstanding inflammatory demyelination; see Shouman et. al. "Focal Sensory Chronic Inflammatory Demyelinating Polyneuropathy (CIDP)" Byline: Kamal Shouman, Divyanshu Dubey, JaNean K. Engelstad, P. James B. Dyck
ABSTRACT
Introduction: For sequential and somatotopic assessment of small fiber neuropathy, heat pain (HP) tests of hypoalgesia might be used instead of decreased counts of epidermal nerve fibers ...(ENFs), but then healthy subject reference values of HP thresholds are needed. Methods: Using the Computer Assisted Sensation Evaluator IVc system, HP thresholds of hypoalgesia were estimated for 10 unilateral sites and counts of ENFs for 4 of them in healthy subjects. Results: In healthy subjects, small but statistically significant differences of both HP thresholds of hypoalgesia and counts of ENFs were observed among tested sites. Significant correlations between HP thresholds and counts of ENFs were not found. Discussion: For the studied somatotopic sites, we provide ≥95th and ≥99th percentile reference limits for HP 0.5 and 5 of 1–10 HP thresholds of hypoalgesia and decreased counts of ENFs at ≤5th and ≤1st percentile levels. Muscle Nerve 58: 509–516, 2018
To study the clinical, electrophysiological and pathological characteristics and outcome of immune-mediated neuropathy (IMN) following stem cell transplantation (SCT).
Retrospective chart review of ...the Mayo Clinic Rochester SCT database between January 1997 and August 2012.
Of the 3305 patients who underwent SCT, 12 patients (0.36%) had IMN. The median time from SCT to IMN was 7 months. IMN typically presented as an asymmetric radiculoplexus neuropathy (7/12 patients) or acute polyradiculoneuropathy (Guillain-Barré syndrome) (4/12). Neurophysiology showed demyelinating neuropathy in four patients and axonal neuropathy in eight. Cerebrospinal fluid protein was increased in five of six patients (median 67 mg/dL). The Neuropathy Impairment Score (NIS) improved in all patients (mean NIS 43-10, p=0.016). Six patients died. One patient died from complications of IMN and one died from complications of the haematological disease. Five patients had recurrence of their malignancy within 4 months of the IMN and of these, four died.
IMN occurs rarely in patients after SCT. Two possible mechanisms include (1) an immune reconstitution syndrome, supported by stereotypical neuropathy types (radiculoplexus and polyradiculoneuropathies), monophasic course and temporal association with SCT and (2) a paraneoplastic phenomenon, supported by frequent early malignancy recurrence following IMN.
To describe the natural history of clinical and laboratory features associated with the m.3243A>G mitochondrial DNA point mutation. Natural history data are needed to obtain prognostic information ...and for clinical trial planning.
We included 85 matrilineal relatives from 35 families with at least 2 visits in this prospective cohort study. Thirty-one were fully symptomatic with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS), and 54 were carrier relatives. Evaluations included standardized questionnaires (medical history and daily living functioning), physical examination, neuropsychological testing, and a battery of imaging and laboratory tests. We evaluated changes in clinical and laboratory features over time and survival. Outcomes are reported over a follow-up period of up to 10.6 years (mean 3.8 ± 2.2 years for patients and 5.5 ± 3.0 for carrier relatives).
Neurologic examination, neuropsychological testing, and daily living scores significantly declined in all patients with MELAS, whereas no significant deterioration occurred in carrier relatives. Cerebral MRI scores declined significantly in patients with MELAS. Magnetic resonance spectroscopy estimates of lactate in the lateral ventricles increased over time, and high lactate was associated with increased mortality. Symptom onset in childhood often was associated with worse outcome. Patients with MELAS had a greater death rate than carrier relatives.
Patients with MELAS carrying the m.3243A>G mutation show a measurable decline in clinical and imaging outcomes. It is hoped that these data will be helpful in anticipating the disease course and in planning clinical trials for MELAS.
Lumbosacral Radiculoplexus Neuropathy (LRPN) is a subacute, painful, paralytic, asymmetric immune-mediated lower-limb neuropathy associated with weight loss and diabetes mellitus (called DLRPN). ...Approximately one-third of LRPN cases have a trigger. Our purpose is to show that COVID-19 can trigger LRPN.
We describe the clinical, neurophysiological, radiologic, and pathologic findings of a 55-year-old man who developed DLRPN after severe acute respiratory syndrome coronavirus-2 infection. Shortly after mild coronavirus disease 2019 (COVID-19), the patient developed severe neuropathic pain (allodynia), postural orthostasis, fatigue, weight loss, and weakness of bilateral lower extremities requiring wheelchair assistance. One month after COVID-19, he was diagnosed with type 2 diabetes mellitus. Neurological examination showed bilateral severe proximal and distal lower extremity weakness, absent tendon reflexes, and pan-modality sensation loss. Electrophysiology demonstrated an asymmetric axonal lumbosacral and thoracic radiculoplexus neuropathies. Magnetic resonance imaging showed enlargement and T2 hyperintensity of the lumbosacral plexus. Cerebral spinal fluid (CSF) showed an elevated protein (138 mg/dL). Right sural nerve biopsy was diagnostic of nerve microvasculitis. He was diagnosed with DLRPN and treated with intravenous methylprednisolone 1 g weekly for 12 weeks. The patient had marked improvement in pain, weakness, and lightheadedness and at the 3-month follow-up was walking unassisted.
COVID-19 can trigger postinfectious inflammatory neuropathies including LRPN.
ABSTRACT
Introduction
Onion‐bulbs (OB) are concentrically layered Schwann‐cell processes, surrounding nerve fibers, occurring in both inherited and acquired demyelinating polyneuropathies. We ...investigated whether OB patterns (generalized, mixed, or focal) correlate with acquired or inherited neuropathies.
Methods
One hundred thirty‐one OB‐rich nerve biopsies were graded for OB pattern and inflammation without knowledge of clinical history. We classified inherited (n = 49) or acquired (n = 82) neuropathies based solely on clinical history.
Results
Fifty‐one biopsies had generalized (34 inherited vs. 17 acquired, P < 0.001), 54 mixed (48 acquired vs. 6 inherited, P < 0.001), and 26 focal/multifocal (inherited n = 9, acquired n = 17) OB. Inflammation occurred more frequently in acquired (n = 54) than inherited (n = 14) neuropathy (P = 0.004).
Discussion
Generalized OB correlates with inherited neuropathy; mixed OB with acquired. Inflammation occurs more in acquired neuropathy cases. OB patterns are best explained by ubiquitous Schwann‐cell involvement in inherited and multifocal Schwann‐cell involvement in acquired neuropathies and predict the electrophysiology of uniform demyelination in inherited and unequal demyelination in acquired neuropathies. Muscle Nerve 59:665–670, 2019
Misdirection of regenerating axons is one of the factors that can explain the poor results often found after nerve injury and repair. In this study, we quantified the degree of misdirection and the ...effect on recovery of function after different types of nerve injury and repair in the rat sciatic nerve model; crush injury, direct coaptation, and autograft repair. Sequential tracing with retrograde labeling of the peroneal nerve before and 8 weeks after nerve injury and repair was performed to quantify the accuracy of motor axon regeneration. Digital video analysis of ankle motion was used to investigate the recovery of function. In addition, serial compound action potential recordings and nerve and muscle morphometry were performed. In our study, accuracy of motor axon regeneration was found to be limited; only 71% (±
4.9%) of the peroneal motoneurons were correctly directed 2 months after sciatic crush injury, 42% (±
4.2%) after direct coaptation, and 25% (±
6.6%) after autograft repair. Recovery of ankle motion was incomplete after all types of nerve injury and repair and demonstrated a disturbed balance of ankle plantar and dorsiflexion. The number of motoneurons from which axons had regenerated was not significantly different from normal. The number of myelinated axons was significantly increased distal to the site of injury. Misdirection of regenerating motor axons is a major factor in the poor recovery of nerves that innervate different muscles. The results of this study can be used as basis for developing new nerve repair techniques that may improve the accuracy of regeneration.
To evaluate the efficacy of dichloroacetate (DCA) in the treatment of mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS).
High levels of ventricular lactate, the ...brain spectroscopic signature of MELAS, correlate with more severe neurologic impairment. The authors hypothesized that chronic cerebral lactic acidosis exacerbates neuronal injury in MELAS and therefore, investigated DCA, a potent lactate-lowering agent, as potential treatment for MELAS.
The authors conducted a double-blind, placebo-controlled, randomized, 3-year cross-over trial of DCA (25 mg/kg/day) in 30 patients (aged 10 to 60 years) with MELAS and the A3243G mutation. Primary outcome measure was a Global Assessment of Treatment Efficacy (GATE) score based on a health-related event inventory, and on neurologic, neuropsychological, and daily living functioning. Biologic outcome measures included venous, CSF, and 1H MRSI-estimated brain lactate. Blood tests and nerve conduction studies were performed to monitor safety.
During the initial 24-month treatment period, 15 of 15 patients randomized to DCA were taken off study medication, compared to 4 of 15 patients randomized to placebo. Study medication was discontinued in 17 of 19 patients because of onset or worsening of peripheral neuropathy. The clinical trial was terminated early because of peripheral nerve toxicity. The mean GATE score was not significantly different between treatment arms.
DCA at 25 mg/kg/day is associated with peripheral nerve toxicity resulting in a high rate of medication discontinuation and early study termination. Under these experimental conditions, the authors were unable to detect any beneficial effect. The findings show that DCA-associated neuropathy overshadows the assessment of any potential benefit in MELAS.
OBJECTIVE:To understand the pathologic and clinical correlates of patients with chronic meralgia paresthetica (MP) undergoing lateral femoral cutaneous nerve (LFCN) neurectomy.
METHODS:A ...retrospective cohort approach was utilized to identify 7 patients undergoing LFCN neurectomy for intractable pain. Control autopsied LFCN was obtained. Clinical, radiologic, and electrophysiologic features were reviewed.
RESULTS:In identified cases, preoperative symptoms included severe lateral thigh pain and numbness. The duration of symptoms prior to surgery ranged from 2 to 15 years. Body mass index (BMI) varied from 20 kg/m to 44.8 kg/m (normal–morbidly obese), with 6 out of 7 patients being obese. No patients were diabetic. Focal nerve indentation at the inguinal ligament was seen intraoperatively and on gross pathology in 4 of 7 cases. Multifocal fiber loss, selective loss of large myelinated fibers, thinly myelinated profiles, regenerating nerve clusters, perineurial thickening, and subperineurial edema were seen. None of these features were observed in control nerve. Morphometric analysis confirmed loss of large myelinated fibers with small and intermediate size fiber predominance. Five patients had varying degrees of intraneural and epineurial inflammation. Six of 7 reported improved pain after neurectomy, sometimes dramatic.
CONCLUSIONS:Patients with chronic MP and intractable pain have an LFCN mononeuropathy with loss of nerve fibers. Pathologic and clinical study supports a compressive pathogenesis as the primary mechanism. Abnormal nerve inflammation coexists and may play a role in pathogenesis. These selected patients typically benefited from neurectomy at a site of inguinal ligament compression.
CLASSIFICATION OF EVIDENCE:This study provides Class IV evidence that patients with chronic MP LFCN neurectomy experience improvement in MP-related pain.
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