Acute to Subacute Atraumatic Entrapment Neuropathies in Patients With CMT1A: A Report of a Distinct Phenotypic Variant of CMT1A.

Charcot-Marie-Tooth type 1A (CMT1A) is typically characterised as a childhood-onset, symmetrical, length-dependent polyneuropathy with a gradual progressive clinical course. Acute to subacute neurological deterioration in CMT1A is rare, and has been reported secondary to overlap pathologies including inflammatory neuropathy. We identified two patients with CMT1A who presented with acute to subacute, atraumatic, entrapment neuropathies as an initial symptom. A superimposed inflammatory neuropathy was excluded. Both patients had a diffuse demyelinating polyneuropathy, with markedly low motor nerve conduction velocities (<20 m/s). In both patients, we demonstrated symptomatic and asymptomatic partial conduction blocks at multiple entrapment sites. Nerve ultrasound findings in our patients demonstrated marked diffuse nerve enlargement, more pronounced at non-entrapment sites compared to entrapment sites. We discuss ways to distinguish this condition from its other differentials. We propose pathophysiological mechanisms underlying this condition. We propose that CMT1A with acute to subacute, atraumatic, entrapment neuropathies to be a distinct phenotypic variant of CMT1A.

Risk factors for lumbosacral radiculoplexus neuropathy.

INTRODUCTION/AIMS: Recently, our group found an association between diabetes mellitus (DM) and lumbosacral radiculoplexus neuropathy (LRPN) in Olmsted County, Minnesota; we found a higher risk (odds ratio [OR], 7.91) for developing LRPN in diabetic compared with nondiabetic patients. However, the influence of other comorbidities and anthropomorphic variables was not studied. METHODS: Demographic and clinical data from 59 LRPN patients and 177 age/sex-matched controls were extracted using the Rochester LRPN epidemiological study. Differences between groups were compared by chi-square/Fisher exact test or Wilcoxon rank-sum test. Uni- and multivariate logistic regression analysis were performed. RESULTS: Factors predictive of LRPN on univariate analysis were DM (OR, 7.91; 95% confidence interval [CI], 4.11-15.21), dementia (OR, 6.36; 95% CI, 1.13-35.67), stroke (OR, 3.81; 95% CI, 1.32-11.01), dyslipidemia (OR, 2.844; 95% CI, 1.53-5.27), comorbid autoimmune disorders (OR, 2.72; 95% CI, 1.07-6.93), hypertension (OR, 2.25; 95% CI, 1.2-4.13), obesity (OR, 2.05; 95% CI, 1.11-3.8), body mass index (BMI) (OR, 1.1; 95% CI, 1.04-1.15), and weight (OR, 1.02; 95% CI, 1.009-1.037). On multivariate logistic regression analysis only DM (OR, 8.03; 95% CI, 3.86-16.7), comorbid autoimmune disorders (OR, 4.58; 95% CI, 1.45-14.7), stroke (OR, 4.13; 95% CI, 1.2-14.25), and BMI (OR, 1.07; 95% CI, 1.01-1.13) were risk factors for LRPN. DISCUSSION: DM is the strongest risk factor for the development of LRPN, followed by comorbid autoimmune disorders, stroke, and higher BMI. Altered metabolism and immune dysfunction seem to be the most influential factors in the development of LRPN.

Hereditary Transthyretin Amyloidosis- Clinical and Genetic Characteristics of a Multiracial South-East Asian Cohort in Singapore.

BACKGROUND AND AIMS: Studies of hereditary transthyretin amyloidosis (ATTRv amyloidosis) in South-East Asia are underrepresented in the literature. We report the unique phenotypic and genetic characteristics of this disorder in a multiracial South-East Asian cohort. METHODS: Patients with genetically proven ATTRv amyloidosis were identified over a 13-year period (2007-2020) at the National Neuroscience Institute, Singapore. Clinical, laboratory, genotypic and electrophysiological features were retrospectively reviewed. RESULTS: 29 patients comprising Chinese, Malay, Burmese, Vietnamese and Indonesians with ATTRv amyloidosis were identified. Somatic neuropathy was the most common initial presentation, followed by carpal tunnel syndrome, autonomic dysfunction and cardiac dysfunction. ATTR-A97S (p.Ala117Ser) was the most common variant found in 14 patients, constituting 66.7%of ethnic Chinese patients and 48.3%of the entire cohort. Five patients had early-onset disease (age < 50 years) with the following variants: ATTR-V30M (p.Val50Met), ATTR-G47A (p.Gly67Ala), ATTR-S50I (p.Ser70Ile) and ATTR-A97S (p.Ala117Ser); one patient with ATTR-A97S (p.Ala117Ser) had isolated unilateral carpal tunnel syndrome with amyloid deposits identified on histological examination of the transverse carpal ligament. All early-onset patients had a positive parental history; two patients, with ATTR-S50I (p.Ser70Ile) and ATTR-Ala97Ser (p.Ala117Ser) respectively, demonstrated anticipation with mother-to-daughter inheritance. Amongst the 24 patients with late-onset disease (age≥50 years), two patients had novel variants, ATTR-G66D (p.Glu86Asp) and ATTR-A81V (p.Ala101Val) that were confirmed to be pathogenic based on the histological identification of transthyretin amyloid. Other identified variants included ATTR-V30M (p.Val50Met), ATTR-R34T (p.Arg54Thr), ATTR-S50I (p.Ser70Ile), ATTR-H88R (p.His108Arg) and ATTR-A97S (p.Ala117Ser). CONCLUSION: Our study further expands the genotypic and phenotypic knowledge regarding ATTRv amyloidosis.

Lumbosacral Radiculoplexus Neuropathy: Neurologic Outcomes and Survival in a Population-Based Study.

OBJECTIVE: To determine whether patients in the community with lumbosacral radiculoplexus neuropathy (LRPN) have milder neuropathy than referral patients, we characterized the outcomes and survival of population-based compared to referral-based LRPN cohorts. BACKGROUND: Previously, we found that the incidence of LRPN is 4.16/100,000/y, a frequency greater than other inflammatory neuropathies. The survival of patients with LRPN is uncharacterized. METHODS: Sixty-two episodes in 59 patients with LRPN were identified over 16 years (2000-2015). Clinical findings were compared to previous referral-based LRPN cohorts. Survival data were compared to those of age- and sex-matched controls. RESULTS: At LRPN diagnosis, median age was 70 years, median Neuropathy Impairment Score (NIS) 22 points, 92% had pain, 95% had weakness, 23% were wheelchair-bound, and median modified Rankin Scale score (mRS) was 3 (range 1-4). At last follow-up, median NIS improved to 17 points (p < 0.001) with 56% having ≥4 points improvement, 16% were wheelchair-bound, and median mRS was 2. Compared to referral-based LRPN cohorts, community patients with LRPN had less impairment, less bilateral disease (37% vs 92%), and less wheelchair usage (23% vs 49%). LRPN survival was 86% at 5 years and 55% at 10 years. Compared to age- and sex-matched controls, patients with LRPN had 76% increased risk of death (p = 0.016). In multivariate analysis, diabetes, age, stroke, chronic kidney disease, peripheral artery disease, and coronary artery disease were significant mortality risk factors but LRPN was not. CONCLUSION: LRPN is a painful, paralytic, asymmetric, monophasic, sometimes bilateral pan-plexopathy that improves over time but leaves patients with impairment. Although having LRPN increases mortality, this increase is probably due to comorbidities (diabetes) rather than LRPN itself.

Lumbosacral radiculoplexus neuropathy: Incidence and the association with diabetes mellitus.

OBJECTIVE: To determine the previously unknown incidence of lumbosacral radiculoplexus neuropathy (LRPN) and its association with diabetes mellitus (DM). METHODS: LRPN defined by clinical and electrophysiologic criteria was identified among Olmsted County, Minnesota, residents during a 16-year period (2000-2015) using the unique facilities of the Rochester Epidemiology Project. DM was ascertained using American Diabetes Association criteria. RESULTS: Of 1,892 medical records reviewed, 59 patients (33 men, 26 women) were identified as having LRPN. The median age was 70 years (range 24-88 years) and the median time of onset of symptoms to diagnosis was 2 months (range 1-72 months). DM was more frequent in patients with LRPN than in controls (39/59 vs 35/177, p < 0.001) but not in those with pre-DM (10/20 vs 55/142, p = 0.336). LRPN recurred in 3 patients with DM resulting in 62 LRPN episodes during the study period. The overall incidence of LRPN was 4.16/100,000/y (95% confidence interval [CI] 3.13-5.18). The incidences of LRPN among DM and non-DM groups were 2.79/100,000/y (95% CI 1.94-3.64) and 1.27/100,000/y (95% CI 0.71-1.83), respectively. The odds of LRPN among patients with DM and pre-DM was 7.91 (95% CI 4.11-15.21) and 1.006 (95% CI 1.004-1.012), respectively. CONCLUSIONS: LRPN incidence in Olmsted County of 4.16/100,000/y makes LRPN a common inflammatory neuropathy and is higher than that of other immune-mediated neuropathies (acute or chronic inflammatory demyelinating polyradiculoneuropathy, brachial plexus neuropathy) assessed within the same population. DM is a major risk factor for LRPN and thus justifies the continued classification of LRPN into diabetic and nondiabetic forms.