The value of MUNIX as an objective electrophysiological biomarker of disease progression in chronic inflammatory demyelinating polyneuropathy.

INTRODUCTION/AIMS: Objective outcome measures to monitor treatment response and guide treatment are lacking in chronic inflammatory demyelinating polyneuropathy (CIDP). In this study we aimed to evaluate the motor unit number index (MUNIX) as an outcome measurement in patients with CIDP and determine the correlation of MUNIX with functional and standard electrodiagnostic tests in a single follow-up study. METHODS: We evaluated MUNIX of the abductor pollicis brevis, abductor digiti minimi, and tibialis anterior (TA) muscles bilaterally. Muscle force was assessed by Medical Research Council Sum Score (MRCSS). Functional measures used were the Overall Neuropathy Limitation Score (ONLS) and the Rasch-built Overall Disability Scale (R-ODS) score at baseline and after 6 months of treatment. Standard electrophysiology was evaluated by the Nerve Conduction Study Score (NCSS). RESULTS: Twenty patients were included at baseline, and 16 completed the follow-up study. Significant correlations were found between the MUNIX sum score and both MRCSS and NCSS at baseline, between both the pinch strength and grip and upper limb MUNIX at baseline and follow-up, and between MUNIX of TA and both lower limb MRCSSs with lower limb ONLS at baseline and follow-up. Significant correlations also were found between MUNIX sum score change and MRCSS change, R-ODS change, and ONLS change. DISCUSSION: MUNIX changes correlated with strength and electrophysiological improvements in CIDP patients. This suggests that MUNIX may represent a useful objective biomarker for patient follow-up.

Screening for thalassemia carriers in populations with a high rate of iron deficiency: revisiting the applicability of the Mentzer Index and the effect of iron deficiency on Hb A2 levels.

Differentiating between ß-thalassemia (ß-thal) minor and iron deficiency has important implications in thalassemia carrier screening. Several complete blood count (CBC)-based equations have been proposed for differentiating these two conditions. The applicability of these equations in populations with high rates of iron deficiency and ß-thal minor, where patients can have both conditions, is limited. In addition, there have been conflicting reports on the possible effect of iron deficiency on Hb A2 level with possible consequences for thalassemia screening programs. Here, we demonstrate that in our population the Mentzer Index separates individuals with ß-thal minor from those without ß-thal minor, regardless of their iron status. Iron deficiency also does not reduce Hb A2 levels in ß-thal minor patients. Correction of iron deficiency is not required for diagnosis of ß-thal minor using high performance liquid chromatography (HPLC).

Evaluation of carotid Intima-Media Thickness (IMT) in amyotrophic lateral sclerosis disease using ultrasonography.

BACKGROUND: Amyotrophic Lateral Sclerosis (ALS) is a progressive neurodegenerative disease with multi-mechanisms as; inflammation, oxidative stress, glutamate excitotoxicity, protein aggregation, etc. This study aimed to evaluate the carotid Intima-Media Thickness (IMT) in ALS and healthy groups, as a possible indicator of these mechanisms. METHODS: 42 patients with ALS along with 53 normal age and body mass index (BMI) matched participants were recruited from the Firoozgar hospital. Carotid IMT values of the participants were measured using B-mode ultrasonography. Using Pearson correlation and logistic regression adjusting with age, BMI, and gender, the IMT values were assessed. RESULTS: The mean right and left carotid IMT values of the ALS patients (0.66 ± 0.09) were significantly higher than normal participants (0.45 ± 0.10) (p < 0.001). In addition, the IMT values were highly correlated with the age (r = 0.632; p < 0.001) and the age of ALS onset (r = 0.595; p < 0.001), in contrast to the BMI. Moreover, the higher value of IMT was associated with an increasing risk of ALS with an odd ratio (OR) of 1.483 (95 % Confidence interval [1.026-2.144]). Eventually, evaluating IMT by classifying ALS patients based on the ALS Health State Scale (ALSHSS) from early to late stage revealed a non-linear increase in the OR (1.372, 1.898, 2.172, and 3.403). CONCLUSION: The increased value of the carotid IMT independent of BMI in ALS could be assessed through ultrasonography as a convenient tool to evaluate the disease severity or possible systemic inflammation.

The Effects of a 10-Week Aerobic and Unilateral Lower Extremity Resistance Training Program on Amplitude and Nerve Conduction Velocity of Sensory and Motor Nerves in Diabetic Patients with Neuropathy.

This study aimed to investigate the effects of 10-week aerobic and unilateral lower extremity resistance training on nerve conduction velocity and amplitude of sensory and motor nerves in diabetic patients with neuropathy. This clinical trial was conducted on twenty women and men (aged 30-60 years old) with diabetic neuropathy. Participants were randomly assigned to one of the two groups: an exercise group (EG; n = 10) and a control group (CG; n = 10). The EG performed a 10-week programme with one session of aerobic exercises (40% to 70% of HR reserve), supplemented with one session of specific lower extremity resistance exercises (60-90 min/day) on the same day for four days per week. The CG subjects performed their regular daily activities. The nerve conduction velocity, amplitude of sensory and motor nerves and glycosylated haemoglobin A1c were measured before and after the intervention. The repeated-measures ANOVA showed a significant increase in the conduction velocity of the sural sensory nerve as well as the peroneal motor nerve (p < 0.01, p < 0.01). The changes in the conduction velocity of the tibial nerve were similar when compared to the control group (p > 0.05). A significantly greater decrease in glycosylated haemoglobin was also observed in the EG group (p < 0.01). Performing 10 weeks of aerobic and specific unilateral lower extremity exercises can improve the function of sensory and motor nerves and improve symptoms in diabetic patients with neuropathy. Given the limited studies in this area, the exact mechanisms of this performance improvement need further examination.

Comparison of Clinical, Ultrasound, and Electrophysiologic Changes in Chronic Inflammatory Demyelinating Polyneuropathy: A Prospective Study.

PURPOSE: The follow-up and monitoring of response to immunomodulatory therapy in patients with chronic inflammatory demyelinating polyneuropathy are still challenging. Various outcome measures have been proposed in recent years, and some are now frequently used in daily clinical practice; however, reliable biomarkers for the disease activity and treatment response are lacking. METHODS: Cross-sectional nerve area of the bilateral vagus, fifth and the sixth cervical spinal, median, ulnar, tibial, peroneal, and sural nerves were measured at 2 time points with an interval of 6 months using nerve ultrasound. The results were used to calculate the ultrasound pattern sumscore (UPSS). The correlation between UPSS change (ΔUPSS) and changes in functional and nerve conduction studies measures over the study period were assessed. RESULTS: Sixteen patients completed this prospective, observational study. General linear model showed that ΔUPSS is significantly associated with ΔMedical Research Council sumscore (ß = -0.72, P = 0.003), Δhandgrip strength (ß = -0.57, P = 0.014), ΔRasch-built overall disability scale (ß = -0.57, P = 0.010), and Δoverall neuropathy limitations scale (ß = 0.75, P < 0.001), after adjustment of confounding variables. Nevertheless, ΔUPSS was not correlated with other clinical measures, including Δpinch power, Δ9-hole peg test, Δ10-m walking test, and Δnerve conduction study sumscore ( P values > 0.05). CONCLUSIONS: Nerve ultrasound might be an efficient method for monitoring the functional status of patients with chronic inflammatory demyelinating polyneuropathy over time because the alterations in its scores could significantly reflect clinical changes.

Acute cerebellitis following COVID-19 vaccination: A case report.

A plethora of neurological symptoms have been reported as the side effects of COVID-19 vaccines. Vaccine-associated acute cerebellitis is quite rare. Here, we report a 45-year-old female with acute onset cerebellitis, beginning 10 days after administration of Sinopharm vaccine. The patient's CSF COVID-19 PCR was found to be positive, with no pulmonary symptoms.

Posterior reversible encephalopathy syndrome in SARS-CoV-2 infection: A case report and review of literature.

Consider PRES in SARS-CoV-2 infected patients who develop encephalopathy, seizures or impaired vision; especially if the disease is complicated by respiratory distress and need for mechanical ventilation.

Iranian clinical practice guideline for amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a rapidly progressive neurodegeneration involving motor neurons. The 3-5 years that patients have to live is marked by day-to-day loss of motor and sometimes cognitive abilities. Enormous amounts of healthcare services and resources are necessary to support patients and their caregivers during this relatively short but burdensome journey. Organization and management of these resources need to best meet patients' expectations and health system efficiency mandates. This can only occur in the setting of multidisciplinary ALS clinics which are known as the gold standard of ALS care worldwide. To introduce this standard to the care of Iranian ALS patients, which is an inevitable quality milestone, a national ALS clinical practice guideline is the necessary first step. The National ALS guideline will serve as the knowledge base for the development of local clinical pathways to guide patient journeys in multidisciplinary ALS clinics. To this end, we gathered a team of national neuromuscular experts as well as experts in related specialties necessary for delivering multidisciplinary care to ALS patients to develop the Iranian ALS clinical practice guideline. Clinical questions were prepared in the Patient, Intervention, Comparison, and Outcome (PICO) format to serve as a guide for the literature search. Considering the lack of adequate national/local studies at this time, a consensus-based approach was taken to evaluate the quality of the retrieved evidence and summarize recommendations.

Iranian Consensus Recommendations for Treatment of Myasthenia Gravis.

Myasthenia gravis (MG) is an immune-mediated potentially treatable disease in which rapid diagnosis and proper treatment can control symptoms. Treatment should be individualized in each patient according to distribution (ocular or generalized) and severity of the weakness, antibody status, thymus pathology, patient comorbidities, and preferences. A group of Iranian neuromuscular specialists have written these recommendations to treat MG based on national conditions. Four of the authors performed an extensive literature review, including PubMed, EMBASE, and Google Scholar, from 1932 to 2020 before the central meeting to define headings and subheadings. The experts held a 2-day session where the primary drafts were discussed point by point. Primary algorithms for the management of MG patients were prepared in the panel discussion. After the panel, the discussions continued in virtual group discussions, and the prepared guideline was finalized after agreement and concordance between the panel members. Finally, a total of 71 expert recommendations were included. We attempted to develop a guideline based on Iran's local requirements. We hope that these guidelines help healthcare professionals in proper treatment and follow-up of patients with MG.

Diagnostic value of high-frequency ultrasound in carpal tunnel syndrome during pregnancy: A case-control study.

Background: Carpal tunnel syndrome (CTS) is the most prevalent entrapment syndrome in the upper limbs, for which pregnancy is a known risk factor. CTS diagnosis is confirmed via nerve conduction studies (NCSs), which sometimes is expensive, and the electrical stimulation makes it an unpleasant diagnostic modality, especially for pregnant subjects. Recently, high-frequency ultrasonography (HF-USG) is known as a diagnostic method. This study is concerned with determining the diagnostic value of this modality for CTS among pregnant women. Methods: This cross-sectional case-control study was conducted with 40 CTS cases and 40 matched controls. The HF-USG of wrists was performed bilaterally on all participants with a focus on the median nerve cross-sectional area (MNCSA) at the carpal tunnel (CT) inlet. Results: Mean MNCSA was statistically different between the CTS group (11.71 ± 1.86 mm2, range: 8 to 18 mm2) and the control group (6.75 ± 1.38 mm2, range: 4 to 11 mm2) (P < 0.001). The receiver operating characteristic (ROC) curve was drawn, and the cross-sectional area (CSA) cut-off point of 8.5 mm2 showed sensitivity and specificity of 98% and 93%, respectively. The positive predictive value (PPV) and the negative predictive value (NPV) were 95% and 98%, respectively, with the mentioned point as the diagnostic threshold. Conclusion: HF-USG of the median nerve can be utilized as a preferable alternative to NCS (the current gold standard diagnostic method) in pregnant women, due to its convenience and lower cost, or at least, it can be used as a screening tool among pregnant women with suspicious symptoms.

Validating the Persian version of the amyotrophic lateral sclerosis-specific quality of life-revised instrument.

Background: Amyotrophic Lateral Sclerosis-Specific Quality of Life-Revised (ALSSQOL-R) encompasses 50 items which assess quality of life (QOL) in patients with amyotrophic lateral sclerosis (ALS) in six major domains. This study aims to translate the ALSSQOL-R into Persian and evaluate its reliability and validity among Iranian patients. Methods: ALSSQOL-R was translated by the standard multi-step forward-backward method. Content validity was calculated using item content validity index (I-CVI). Three items in the "intimacy" domain were deleted considering Iranian culture. Cronbach's alpha was used for all 6 dimensions to calculate the internal consistency reliability. Test-retest reliability was evaluated using intraclass correlation coefficient (ICC) with one-month interval. Concurrent validity was measured by the validated version of 36-Item Short Form Health Survey (SF-36) questionnaire. Results: Sixty-three patients with ALS were enrolled in the study. I-CVI was 70%, promoted to 85% after modifications (acceptable). Regarding internal consistency reliability, Cronbach's alpha in all six domains was 0.70 and total Cronbach's alpha was 0.89 which is assumed as good. In terms of test-retest reliability, ICC [95% confidence interval (CI)] was 0.91 (91%) and Pearson correlation coefficient (r) was 0.90 (P < 0.001), all indicating an excellent reliability. The concurrent validity was established based on a strong correlation with SF-36 (r = 0.744, P < 0.001). Conclusion: The findings show that the modified Persian version of ALSSQOL-R is a valid and reliable QOL questionnaire which can be used for Iranian patients with ALS in both clinical and research settings.

Myasthenia gravis associated with novel coronavirus 2019 infection: A report of three cases.

Several neurological presentations have been reported following coronavirus 2019 (COVID-19) infection. This case report describes three myasthenia gravis (MG) patients presented following COVID-19 infection. We report three adult patients with myasthenic Gravis and COVID-19 infection. The patients are between 38 and 61 years old. Case 1 is a 61-year-old woman with progressive dysphagia, nasal speech, ocular ptosis, diplopia, and proximal muscle weakness for 10 days. She had a COVID-19 infection 6 weeks ago. Case 2 is a 57-year-old man with clinical symptoms of muscular fatigability, diplopia, ptosis, and dysphagia for a week and a positive COVID-19 infection 10 days ago. Case 3 is a 38-year-old woman with fatigability, ptosis, dysphagia, and a diagnosis of COVID-19 infection 4 weeks ago. All patients had a positive RT-PCR for COVID-19 infection by nasopharyngeal swab test and a high-level acetylcholine receptor antibody in the serum. All patients were treated with pyridostigmine and prednisolone with a favorable outcome. MG may appear following COVID-19 infection, and the role of molecular mimicry and latent MG activation should be considered the cause of the disease onset.

Application of CMAP scan for the evaluation of patients with chronic inflammatory demyelinating polyneuropathy: a prospective study.

AIMS: We aimed to assess the compound muscle action potential (CMAP) scan in the follow-up of chronic inflammatory demyelinating polyneuropathy (CIDP) patients and investigate the correlation of CMAP scan parameters with functional and standard electrodiagnostic tests. METHODS: We evaluated four parameters of abductor pollicis brevis (APB) CMAP scan (i.e., step numbers, step percentage, S10, S90), functional measures (e.g., Medical Research Council Sum Scores), and electrodiagnostic tests, including nerve conduction study (NCS) and motor NCS of the median nerve in the baseline and after six months of treatment. RESULTS: Twenty patients completed baseline clinical and electrodiagnostic studies. However, sixteen patients completed the follow-up study. The median of step numbers at baseline was 3.5 (2-4.2), which decreased to 2.5 (0-3) (p = 0.005). After the treatment, step percentage reduced from 28.6 (23.9-38.7) to 13.4 (0-23.6) (p = 0.001). The scores obtained from the clinical scales showed significant recovery of most of the functions, while the alterations of NCSS and NCS of the median nerve were not significant. CONCLUSIONS: We found a significant reduction in step number and step percentage after follow-up. This alteration was not reflected in standard electrodiagnostic values. The improvement of functional scales alongside the CMAP scan parameters suggests that the CMAP scan could be considered an appropriate outcome measurement in research and clinical fields.

Recommendations for Infantile-Onset and Late-Onset Pompe Disease: An Iranian Consensus.

Background: Pompe disease, also denoted as acid maltase or acid α-glucosidase deficiency or glycogen storage disease type II, is a rare, autosomal recessive lysosomal storage disorder. Several reports have previously described Pompe disease in Iran and considering increased awareness of related subspecialties and physicians, the disease's diagnosis is growing. Objective: This guideline's main objective was to develop a national guideline for Pompe disease based on national and international evidence adapting with national necessities. Methods: A group of expert clinicians with particular interests and experience in diagnosing and managing Pompe disease participated in developing this guideline. This group included adult neurologists, pediatric neurologists, pulmonologists, endocrinologists, cardiologists, pathologists, and physiatrists. After developing search terms, four authors performed an extensive literature review, including Embase, PubMed, and Google Scholar, from 1932 to current publications before the main meeting. Before the main consensus session, each panel member prepared an initial draft according to pertinent data in diagnosis and management and was presented in the panel discussion. Primary algorithms for the diagnosis and management of patients were prepared in the panel discussion. The prepared consensus was finalized after agreement and concordance between the panel members. Conclusion: Herein, we attempted to develop a consensus based on Iran's local requirements. The authors hope that disseminating these consensuses will help healthcare professionals in Iran achieve the diagnosis, suitable treatment, and better follow-up of patients with infantile-onset Pompe disease and late-onset Pompe disease.

Zytux in Refractory Myasthenia Gravis: A Multicenter, Open-Labeled, Clinical Trial Study of Effectiveness and Safety of a Rituximab Biosimilar.

Objectives: Myasthenia gravis (MG) is an immune-mediated neuromuscular disorder responsive to immunomodulatory treatments. 10-20% of MGs are not responsive to conventional first-line therapies. Here, we sought to investigate the efficacy and safety of rituximab therapy in the treatment of patients with refractory MG. Methods: In a 48-week, multicenter, open-labeled, prospective cohort setting, 34 participants with refractory MG were assigned to receive infusions of Zytux, which is a rituximab biosimilar, according to a validated protocol. Clinical, functional, and quality of life (QoL) measurements were recorded at baseline, and seven further visits using the Myasthenia Gravis Foundation of America (MGFA), Myasthenia Gravis Composite (MGC), Myasthenia Gravis Activities of Daily Living profile (MG-ADL), and Myasthenia Gravis Quality of Life (MGQoL-15) scales. Besides, the post-infusion side effects were systematically assessed throughout the study. Results: The correlation analysis performed by generalized estimating equations analysis represented a significant reduction of MGC, MG-ADL, and MGQoL-15 scores across the trial period. The subgroup analysis based on the patients' clinical status indicated a significant effect for the interaction between time and MGFA subtypes on MG-ADL score, MGC score, and pyridostigmine prednisolone dose, reflecting that the worse clinical condition was associated with a better response to rituximab. Finally, no serious adverse event was documented. Conclusions: Rituximab therapy could improve clinical, functional, and QoL in patients with refractory MG in a safe setting. Further investigations with larger sample size and a more extended follow-up period are warranted to confirm this finding. Clinical Trial Registration: The study was registered by the Iranian Registry of Clinical Trials (IRCT) (Code No: IRCT20150303021315N18).

Facing COVID-19, Jumping From In-Person Training To Virtual Learning: A Review on Educational and Clinical Activities in a Neurology Department.

The new coronavirus virus 2019 (COVID-19) has affected many routine medical activities, including medical education and clinical activities. The social isolation has led to highlighting virtual learning and telemedicine. We present a report of our adoptive procedures taken during the outbreak of COVID-19 in our tertiary healthcare center and compare the current educational and clinical issues with these issues one month before the outbreak. Virtual learning is a useful replacement in this critical situation.

Guillain-Barre syndrome in patients with coronavirus disease-2019: Report of six cases and review of literature.

Background: Few studies have reported the association of Guillain-Barre syndrome (GBS) and coronavirus disease-2019 (COVID-19) infection. In this study, we reported GBS in six patients infected with COVID-19 and reviewed all existing literature about GBS in association with COVID-19. Methods: This study was performed in three referral centers of COVID-19 in Iran, and six patients with the diagnosis of GBS were enrolled. Patients enrolled in the study with acute progressive weakness according to the demyelinating or axonal variant of GBS, according to Uncini's criteria. Results: Four of our patients had axonal polyneuropathy, two patients had demyelinating polyneuropathy, and one patient required mechanical ventilation. All our patients had a favorable response to treatment. In one patient, the GBS symptoms recurred four months after the first episode. Conclusion: Limited case reports suggest a possible association between GBS and COVID-19. Such associations may be an incidental concurrence or a real cause-and-effect linkage; however, more patients with epidemiological studies are necessary to support a causal relationship.

Description of combined ARHSP/JALS phenotype in some patients with SPG11 mutations.

BACKGROUND: SPG11 mutations can cause autosomal recessive hereditary spastic paraplegia (ARHSP) and juvenile amyotrophic lateral sclerosis (JALS). Because these diseases share some clinical presentations and both can be caused by SPG11 mutations, it was considered that definitive diagnosis may not be straight forward. METHODS: The DNAs of referred ARHSP and JALS patients were exome sequenced. Clinical data of patients with SPG11 mutations were gathered by interviews and neurological examinations including electrodiagnosis (EDX) and magnetic resonance imaging (MRI). RESULTS: Eight probands with SPG11 mutations were identified. Two mutations are novel. Among seven Iranian probands, six carried the p.Glu1026Argfs*4-causing mutation. All eight patients had features known to be present in both ARHSP and JALS. Additionally and surprisingly, presence of both thin corpus callosum (TCC) on MRI and motor neuronopathy were also observed in seven patients. These presentations are, respectively, key suggestive features of ARHSP and JALS. CONCLUSION: We suggest that rather than ARHSP or JALS, combined ARHSP/JALS is the appropriate description of seven patients studied. Criteria for ARHSP, JALS, and combined ARHSP/JALS designations among patients with SPG11 mutations are suggested. The importance of performing both EDX and MRI is emphasized. Initial screening for p.Glu1026Argfs*4 may facilitate SPG11 screenings in Iranian patients.

A Mitochondrial Disorder in a Middle Age Iranian Patient: Report of a Rare Case.

INTRODUCTION: Mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) can involve multiple systems and cause stroke-like episodes and status epilepticus. CASE PRESENTATION: A 48-year-old female with history of early fatigability, migraine-type headaches, and bilateral sensory-neural hearing loss presented 3 episodes of serial seizures. On admission she was affected by Wernicke aphasia and, then, right hemiparesis. Investigations showed elevated arterial lactate and ragged red fibers on muscle biopsy. CONCLUSION: Though more commonly diagnosed during childhood, some cases of adult-onset MELAS syndrome are reported. This syndrome should be considered in patients with stroke-like events in adults without cerebrovascular risk factors and difficult-to-treat seizures.