The spectrum of rippling muscle disease.

Rippling muscle disease (RMD) is a rare disorder of muscle hyperexcitability. It is characterized by rippling wave-like muscle contractions induced by mechanical stretch or voluntary contraction followed by sudden stretch, painful muscle stiffness, percussion-induced rapid muscle contraction (PIRC), and percussion-induced muscle mounding (PIMM). RMD can be hereditary (hRMD) or immune-mediated (iRMD). hRMD is caused by pathogenic variants in caveolin-3 (CAV3) or caveolae-associated protein 1/ polymerase I and transcript release factor (CAVIN1/PTRF). CAV3 pathogenic variants are autosomal dominant or less frequently recessive while CAVIN1/PTRF pathogenic variants are autosomal recessive. CAV3-RMD manifests with a wide spectrum of clinical phenotypes, ranging from asymptomatic creatine kinase elevation to severe muscle weakness. Overlapping phenotypes are common. Muscle caveolin-3 immunoreactivity is often absent or diffusely reduced in CAV3-RMD. CAVIN1/PTRF-RMD is characterized by congenital generalized lipodystrophy (CGL, type 4) and often accompanied by several extra-skeletal muscle manifestations. Muscle cavin-1/PTRF immunoreactivity is absent or reduced while caveolin-3 immunoreactivity is reduced, often in a patchy way, in CAVIN1/PTRF-RMD. iRMD is often accompanied by other autoimmune disorders, including myasthenia gravis. Anti-cavin-4 antibodies are the serological marker while the mosaic expression of caveolin-3 and cavin-4 is the pathological feature of iRMD. Most patients with iRMD respond to immunotherapy. Rippling, PIRC, and PIMM are usually electrically silent. Different pathogenic mechanisms have been postulated to explain the disease mechanisms. In this article, we review the spectrum of hRMD and iRMD, including clinical phenotypes, electrophysiological characteristics, myopathological findings, and pathogenesis.

Autonomic impairment in primary lateral sclerosis.

PURPOSE: Prior studies reported evidence of autonomic involvement in motor neuron disease and suggested more severe dysfunction in upper motor neuron predominant syndromes. Hence, we sought to characterize autonomic impairment in primary lateral sclerosis. METHODS: Neurological evaluations, thermoregulatory sweat tests, and autonomic reflex screens were analyzed retrospectively in 34 primary lateral sclerosis patients (28 definite and 6 probable). Patients with other potential causes of autonomic failure and patients with autonomic testing results compromised by artifact were excluded. RESULTS: A total of 17 patients reported autonomic symptoms. Orthostatic lightheadedness was most frequent (8 patients), followed by bladder (7), bowel (5), and erectile dysfunction (3). The autonomic reflex screens of 33 patients were reviewed; 20 patients had abnormal studies. The thermoregulatory sweat tests of 19 patients were reviewed; 11 patients had abnormal studies. Composite Autonomic Severity Score was calculated for 33 patients and found abnormal in 20/33 patients (60.6%): 15/20 patients (75%) had mild impairment, and 5/20 patients (25%) had moderate impairment. The frequencies of testing abnormalities were: sudomotor 18/20 (90%), cardiovagal 9/20 (45%), and adrenergic 6/20 (30%). Sweat loss pattern analysis showed global, regional, and mixed patterns to be more common than length-dependent and distal patterns. CONCLUSION: We found evidence of frequent autonomic dysfunction in primary lateral sclerosis, which is generally of modest severity akin to prior reports for amyotrophic lateral sclerosis, but more commonly in a pattern consistent with preganglionic/ganglionic localization. This suggests that primary lateral sclerosis, as with amyotrophic lateral sclerosis, is a multisystem disease that affects the autonomic nervous system.

Egyptian adaptation and validation of the Edinburgh Cognitive and Behavioral Amyotrophic Lateral Sclerosis Screen (ECAS-EG).

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is the most common, fatal adult neuromuscular disease. It is a multi-system disorder characterized primarily by motor manifestations, but there is established evidence for cognitive and behavioral impairment, which is associated with poor prognosis, hence, the importance of tools for its assessment. The Edinburgh Cognitive and Behavioral Assessment Screen (ECAS) is an invaluable assessment tool for cognition in ALS-front temporal spectrum dementia (FTSD), as it accommodates physical challenges that usually confound traditional neuropsychological testing in those patients. OBJECTIVE AND METHODS: To validate the Egyptian Arabic version of ECAS (ECAS-EG) based on the original English scale. This is a prospective study. The ECAS was adapted and administered to 62 Egyptian ALS patients and 60 healthy controls. Patients were recruited from the Neuromuscular Unit, Ain Shams University Hospital. The ECAS was adapted to Egyptian Arabic after being translated using the back translation method. Internal consistency of the test, inter-rater reliability, and construct validity were assessed. RESULTS: The Egyptian Arabic version of ECAS (ECAS-EG) showed good internal consistency using Cronbach's alpha of 0.84. Inter-rater reliability was tested, values for all variables were compared, and no statistically significant differences were found (ICC = .997). ECAS-EG discriminated significantly between the patients from the control subjects (p-value of 0.001). There was a strong positive correlation between the ECAS-EG total score and the MoCA total score with a p-value of 0.001, thus indicating convergent validity. The test showed that 63% of Egyptian ALS patients were cognitively affected; most affected domains were executive functions and verbal fluency. CONCLUSION: The current study proves that the Egyptian version of the ECAS (ECAS-EG) is valid and reliable among Egyptian ALS patients and it would be applicable to the general Arabic-speaking population.

Relationship of glycaemic derangement using continuous glucose monitoring system with sleep pattern among children with type 1 diabetes.

BACKGROUND: Glycaemic derangement has been linked to sleep disruption. However, the impact of glycaemic derangement on sleep pattern among children with type 1 diabetes (C-T1D) remains unraveled. AIM: To assess the effect of nocturnal hyperglycaemia and clinically significant (CS) hypoglycaemia on sleep pattern among C-T1D. METHODOLOGY: Thirty C-T1D were compared to 30 age and sex matched healthy siblings. Patients having other organ disease that might cause sleep disorders or on medications causing sleep disturbance were excluded. History included diabetes-duration, type and dose of insulin therapy, chronic diabetic-complications, and manifestations of sleep disorders. Epworth Sleepiness Scale-Child Adolescent was used. Continuous glucose monitoring system (CGMS) and overnight polysomnography were done and analysed. RESULTS: C-T1D had significantly lower sleep efficiency and significantly higher arousal index (AI), periodic limb movement index and apnoea-hypopnoea index compared to controls. Moreover, they had significantly longer sleep-onset latency, light sleep percentage, and shorter rapid eye movement percentage than controls. According to nocturnal CGMS readings, 15 C-T1D had nocturnal hyperglycaemia (50%), six experienced CS hypoglycaemia (20%), two had level-1 hypoglycaemia (6.7%), and seven were within the normoglycaemic range (23.3%). C-T1D experiencing nocturnal CS hypoglycaemia had significantly higher stage 3 sleep (P = 0.004) than controls. On the other hand, C- T1D experiencing nocturnal hyperglycaemia had significantly higher sleep onset latency (P = 0.013), light sleep percentage (P < 0.001), and AI (P < 0.001) than controls. Nocturnal CS hypoglycaemia was positively correlated to deep sleep duration, while hyperglycaemia was correlated to number of awakenings, sleep-onset latency, and light sleep duration. CONCLUSION: In children with T1D CS hypoglycaemia is associated with sleep deepening, while hyperglycaemia is associated with increased light sleep, sleep onset latency.

Nerve transcriptomes in autoimmune and genetic demyelinating neuropathies: Pathogenic pathway assessment of nerve demyelination.

The pathogenesis of autoimmune demyelinating neuropathies is poorly understood compared to inherited demyelinating forms. We performed whole transcriptome (RNA-Seq) using nerve biopsy tissues of patients with different autoimmune and inherited demyelinating neuropathies (CIDP n = 10, POEMS n = 18, DADS n = 3, CMT1 n = 3) versus healthy controls (n = 6). A limited number of differentially expressed genes compared to healthy controls were identified (POEMS = 125, DADS = 15, CMT = 14, CIDP = 5). Divergent pathogenic pathways including inflammatory, demyelinating and neurite regeneration such as with the triggering receptor expressed on myeloid cells (TREM1) part of the immunoglobulin superfamily and RhoGD1 are found. Shared and discordant pathogenic injury are discovered between autoimmune and inherited forms.

How COVID-19 pandemic changed our management strategies for amyotrophic lateral sclerosis (ALS) patients: Egyptian study.

BACKGROUND: There are several studies that have discussed the efficacy of telemedicine with amyotrophic lateral sclerosis (ALS) patients; however, this approach is still preliminary in Egypt and in North Africa. The objective of the current study is to discuss current experience with telemedicine in monitoring patients in the specialized ALS clinic in Egypt. Efficacy of Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) in monitoring disease progression remotely will be discussed. RESULTS: This is a prospective study. Forty-three ALS patients were included in this study in the period between July 1, 2020, and February 6, 2021. Fifty-three telemedicine encounters and 13 post-telemedicine office visits were available. None of the participating patients had COVID-19 infection. Eight patients showed decline in ALSFRS score. ALSFRS-R score reported during telemedicine encounters was confirmed during office visits. Three bulbar onset ALS patients had gastrostomy, and 2 bulbar onset ALS patients had Botox injection for drooling. All eight patients with declining ALSFRS-R were maintained on non-invasive ventilation (NIV) based on their symptoms. CONCLUSION: This is the first study discussing telemedicine in the field of ALS in Egypt and North Africa. ALSFRS-R showed feasibility and reliability in detecting disease progression remotely.

Arabic adaptation and validation of the revised amyotrophic lateral sclerosis functional rating scale (ALSFRS-R): Egyptian study.

INTRODUCTION: ALSFRS-R is 12-item scale used to assess disability and to measure disease progression in ALS patients. The objective is to validate the Arabic version of ALSFRS-R based on the original English version. Methods and patients: This is a cross sectional study. ALSFRS-R was administered to 162 Egyptian patients with ALS after being translated in Arabic, and reapplied after 1 week. Patients were recruited from 2 centers: Neuromuscular unit, Ain Shams University hospitals and the specialized ALS clinic which is located at the international medical center (IMC). Results: No significant differences were found between the application and reapplication of the scale (p = 0.5). The linear regression and internal consistency that were measured by Pearson correlation and alpha Conbrach respectively were significant. Discussion: The Arabic version of the ALSFRS-R proposed by the current was proven to be reproducible and valid among Egyptian ALS patients. Thus, it will provide a useful tool for professionals to evaluate Arabic speaking patients in clinical practice and research.

Disturbed sleep quality and architecture in adolescents with type 1 diabetes mellitus: Relation to glycemic control, vascular complications and insulin sensitivity.

BACKGROUND: Insufficient sleep duration and poor sleep quality have been linked to insulin resistance and impaired glucose metabolism. However, the relation between sleep disruption and type1 diabetes (T1D) hasn't been thoroughly explored. AIM: To study the association between sleep parameters and glycemic control, insulin resistance and micro-vascular complications among adolescent with T1D. METHODOLOGY: Sixty adolescents with T1D were compared to 60 matched controls. Diabetes-duration, insulin-therapy, fundus, Epworth Sleepiness Scale-Child Adolescent and the neuropathy disability score were assessed. Fasting lipids, fraction-C of glycosylated hemoglobin(HbA1c) and urinary albumin-excretion were measured with calculation of the insulin sensitivity score(ISS). Overnight polysomnography(PSG) was done. RESULTS: Adolescents with T1D had significantly lower sleep efficiency and rapid eye movement(REM) sleep than controls with significantly higher sleep onset latency, non-REM sleep and arousal index(P < 0.001). Although ISS was negatively correlated to total sleep time(P = 0.002); it was positively correlated to sleep efficiency(P < 0.001). HbA1C was negatively correlated to sleep efficiency(<0.001) and REM sleep(P = 0.003) and positively correlated to sleep onset latency(P = 0.005). T1D adolescents with micro-vascular complications had significantly lower sleep efficiency and REM sleep than those without micro-vascular complications. CONCLUSION: Poor sleep quality and architecture among adolescents with T1D are associated with impaired glycemic control, insulin resistance and micro-vascular complications.

Assessment of diagnostic potential of some circulating microRNAs in Amyotrophic Lateral Sclerosis Patients, an Egyptian study.

OBJECTIVE: Numerous studies have been carried out to identify the role of microRNA (miRNA) as potential biomarkers for many diseases including amyotrophic lateral sclerosis (ALS). The aim of this study was to explore the circulating levels of some miRNAs in cohort of Egyptian ALS patients in an attempt to correlate the selected miRNA profiles with disease progression. METHODS: Thirty ALS patients and 20 age and sex matched healthy controls were enrolled. Circulating miRNA levels were determined in venous blood samples, collected on EDTA, from all the study subjects. The selection of miRNA species (miR-206, miR-142-3p, miR-143-3p, miR-181a-5p, miR-106b-3p, miR-4516 and Let7f-5p) was based on their involvement in the pathophysiology of ALS and was further confirmed by data mining of specific miRNA databases (miRBase and miRDB). RESULTS: As compared to the control group, significant consistent upregulation was found in the levels of miR-206, miR-143-3p and to a lesser extent in miR-142-3p. An elevation trend, although not significant, was also found in the levels of miR-181a-5p, miR-106b-3p, and miR-4516. Interestingly, we found that the levels of miR-142-3p were elevated in familial cases, while that of miR-4516 were significantly increased in sporadic cases. Furthermore, the levels of Let7f-5p, although were generally lowered in ALS patients but were also decreased in familial cases as well as in spinal onset ALS as compared to bulbar onset. CONCLUSION: This is the first study investigating miRNA profiles in Egyptian ALS patients. We found that some miRNAs are significantly altered in ALS patients, and some may be used to distinguish familial and sporadic cases and bulbar and spinal onset. Larger study is needed, in which we will conduct a correlation of miRNA levels against variations in disease onset, progression as well as systemic inflammatory responses and the extent of neuromuscular involvement in Egyptian ALS patients in an attempt to identify environmental/occupational risk factors.

Diagnostic delay among ALS patients: Egyptian study.

Introduction: In the current study, we are going to look at different factors responsible for the diagnostic delay of ALS patients among the sample of Egyptian patients. Method/patients: This is a cohort study. ALS patients were recruited from December 2018 to January 2020 from the ALS clinic at the international medical center (IMC) (Cairo, Egypt). We analyzed the site of onset, the time from symptom onset to diagnosis, age and sex differences among these ALS patients. Results: Thirty patients were included in the study. Seventy percent of the patients had limb onset ALS with a mean age of onset of 50 ± 12.1 vs 58.6 ± 2.1 years for the patients with bulbar onset (p = 0.02). Bulbar-onset patients were diagnosed earlier than limb onset patients (mean lag of 8.2 ± 2.57 months vs 22.95 ± 17.6 months respectively, p < 0.05). The average diagnosis time for women was slightly longer than that of men with a mean lag of 20.7 ± 21.1 vs. 17.6 ± 13.6 months, respectively, p > 0.05. Diagnostic delay and age at onset of symptoms were negatively correlated, however, this was not statistically significant. Discussion: To our knowledge, this the first population-based study from Egypt about predicting factors of diagnostic delay among Egyptian patients. Limb onset, female gender and young age are correlated with increased mean time to diagnosis. Statistically insignificant results could be attributed to a small sample. Larger population-based studies are needed from Egypt.