Clinical and genetic evaluation of hereditary myopathies in an adult Saudi cohort.

BACKGROUND: Diagnosis of hereditary myopathy is often challenging owing to overlapping clinical phenotypes and muscle histopathological findings. This retrospective study aimed to identify the phenotypic and genotypic spectra of hereditary myopathies at a tertiary hospital in Riyadh, Saudi Arabia. METHODS: We reviewed the medical records of patients with hereditary myopathy who were evaluated between January 2018 and December 2022. RESULTS: Eighty-seven patients (78 families) were included, two-thirds were men with a mean age of 35 (SD 14.2) years. Limb-girdle muscular dystrophy (LGMD) was the most prevalent clinical diagnosis (25 cases; 29%), of whom, a genetic diagnosis was achieved in 15 of 22 patients tested (68%). In genetically confirmed LGMD, the most prevalent disorders were dysferlinopathy (27%) followed by fukutin-related protein (FKRP) - related limb girdle muscular dystrophy (20%), sarcoglycanopathy (20%), lamin A/C related myopathy (13%), and calpain-3 myopathy (13%). In 26 patients with pathogenic/likely pathogenic variants, the genetic testing method was whole exome sequencing (WES) (42%), Next generation sequencing (NGS) (31%), and targeted single gene analysis (27%). The sensitivity of each genetic testing method was as follows: 100% for targeted single-gene analysis, 100% for targeted analysis of D4Z4 repeat array units, 88% for myotonic dystrophy protein kinase (DMPK) repeat expansion analysis, 42% for NGS-neuromuscular panel, and 46% for WES. CONCLUSION: The prevalent types of hereditary myopathies were consistent with those reported locally and internationally. This study highlights the diagnostic yield of various molecular genetic tests for the diagnosis of hereditary myopathy in an adult cohort and the need for improved access to advanced molecular testing in cases suspected to have facioscapulohumeral muscular dystrophy (FSHD) or mitochondrial myopathies.

Translation and validation of the Arabic version of the Boston carpal tunnel syndrome questionnaire.

OBJECTIVE: To translate and validate the Arabic version of the Boston carpal tunnel questionnaire (BCTQ-A). METHODS: We recruited consecutive patients with carpal tunnel syndrome (CTS). Reliability was assessed with Cronbach alpha, reproducibility with intraclass correlation coefficients, construct validity with factor analysis, and responsiveness post carpal tunnel release (CTR) with the Wilcoxon signed-rank test. RESULTS: In 134 patients, the mean total scores for the symptom severity scale (SSS) and functional status scale (FSS) were 32.0+/-8.4 (alpha=0.88, ICC=0.88) and 18.5+/-7.6 (alpha=0.87, ICC=0.89), respectively. As in the original Boston carpal tunnel questionnaire (BCTQ), a 3-factor model of the BCTQ-A best fitted the data. The BCTQ-A, SSS, and FSS scores were significantly lower post-CTR. CONCLUSION: The BCTQ-A is reliable, valid, reproducible, and responsive to interventions. The Arabic version can be now used with Arabic-speaking patients with CTS.

Frequent laboratory abnormalities in CIDP patients.

INTRODUCTION: The role of screening laboratory tests in chronic inflammatory demyelinating polyneuropathy (CIDP) is currently unknown. The objectives of this study are to explore common laboratory test abnormalities in CIDP patients. METHODS: CIDP subjects attending the Neuromuscular Clinic between 01/2013 and 12/2014 were evaluated. Demographic data, clinical history, physical examination, and laboratory test results were extracted from their charts. RESULTS: Seventy-nine charts were reviewed. Mean age was 61 ± 11 years. Most (84%) CIDP patients had laboratory test abnormalities; the most frequent were paraproteinemia (29%) and elevated HbA1C (28%) and creatine kinase (27%). Additional abnormalities included anemia in 19%, and elevated anti-neutrophil cytoplasmic antibody, erythrocyte sedimentation rate, and urate in 17%, elevated antinuclear antibodies, rheumatoid factor, and thyroid-stimulating hormone in 11%, and abnormal C3 in 10%. CONCLUSIONS: Laboratory test abnormalities were found in most CIDP patients. The most common were paraproteinemia, higher than expected frequency of diabetes, and unexpected CK elevation. Additional abnormalities included anemia, high urate levels, and common biomarkers for vasculitic neuropathies. Muscle Nerve 53: 862-865, 2016.

A timed Phalen's test predicts abnormal electrophysiology in carpal tunnel syndrome.

OBJECTIVE: Previous studies reported variable sensitivity and specificity of the Phalen test. We investigated whether a timed Phalen's test (TPT) could predict abnormal nerve conduction studies (NCS) results in carpal tunnel syndrome (CTS). METHODS: Patients with CTS were consecutively recruited. A neurologist confirmed the clinical diagnosis of CTS and recorded the TPT before NCS were performed. Another neurologist, blinded to the TPT, graded the severity of NCS. The TPT sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated. RESULTS: In total, 403 patients with 706 hands were recruited and diagnosed with CTS; 465 hands had positive TPT, and 611 hands showed abnormal NCS results. A positive TPT at ≤ 10 s had a specificity of 96.8% and a PPV of 96.6% in predicting abnormal NCS. The sensitivity and NPV of TPT were insignificant. DISCUSSION: A positive TPT at ≤ 10 s can be useful in predicting NCS abnormalities in patients with CTS.

The sensitivity and specificity of the neurological examination in polyneuropathy patients with clinical and electrophysiological correlations.

INTRODUCTION: Polyneuropathy is one of the most prevalent neurologic disorders. Although several studies explored the role of the neurological examination in polyneuropathy, they were mostly restricted to specific subgroups of patients and have not correlated examination findings with symptoms and electrophysiological results. OBJECTIVES: To explore the sensitivity and specificity of different neurological examination components in patients with diverse etiologies for polyneuropathy, find the most sensitive combination of examination components for polyneuropathy detection, and correlate examination findings with symptoms and electrophysiological results. METHODS: Patients with polyneuropathy attending the neuromuscular clinic from 01/2013 to 09/2015 were evaluated. Inclusion criteria included symptomatic polyneuropathy, which was confirmed by electrophysiological studies. 47 subjects with no symptoms or electrophysiological findings suggestive for polyneuropathy, served as controls. RESULTS: The total cohort included 312 polyneuropathy patients, with a mean age of 60±14 years. Abnormal examination was found in 95%, most commonly sensory findings (86%). The most common abnormal examination components were impaired ankle reflexes (74%), vibration (73%), and pinprick (72%) sensation. Combining ankle reflex examination with vibration or pinprick perception had the highest sensitivity, of 88%. The specificities of individual examination component were generally high, excluding ankle reflexes (62%), and vibration perception (77%). Abnormal examination findings were correlated with symptomatic weakness and worse electrophysiological parameters. CONCLUSION: The neurological examination is a valid, sensitive and specific tool for diagnosing polyneuropathy, and findings correlate with polyneuropathy severity. Ankle reflex examination combined with either vibration or pinprick sensory testing is the most sensitive combination for diagnosing polyneuropathy, and should be considered minimal essential components of the physical examination in patients with suspected polyneuropathy.

Disease activity in chronic inflammatory demyelinating polyneuropathy.

INTRODUCTION: Evaluation of disease status in patients with chronic inflammatory demyelinating polyneuropathy (CIDP) is often done by a combination of clinical evaluation and electrodiagnostic studies. A CIDP disease activity status (CDAS) was developed to standardize outcomes in CIDP patients. We aimed to determine if the CDAS was concordant with classical evaluation and whether CDAS enables benchmarking of CIDP. METHODS: We performed a retrospective chart review of 305 CIDP patients and identified 206 patients with >1 visit and applied the CDAS to this cohort. We examined relationships between the CDAS and classical evaluation as to outcomes and compared our cohort to other CIDP cohorts who had CDAS. RESULTS: We found that the CDAS mirrored disease severity as measured by electrophysiology and vibration perception thresholds in that CDAS class 5 had more severe neuropathy. Our results are similar to other cohorts in the middle CDAS strata with the exception of fewer subjects in CDAS 1 and more in CDAS 5. The only demographic factor predicting CDAS 5 in our cohort was age, and the overall treatment response rate using the CDAS classification was 79.3%. CONCLUSIONS: CDAS appears to have sufficient face-validity as a grading system to assess disease activity in relation to treatment status. The use of CDAS appears to allow benchmarking of patients with CIDP that may be useful in subject selection for clinical trials and also to highlight differences in practice.

Elevated Vibration Perception Thresholds in CIDP Patients Indicate More Severe Neuropathy and Lower Treatment Response Rates.

INTRODUCTION: Vibration perception threshold (VPT) examination using a neurothesiometer provides objective, sensitive and specific information, and has been utilized mainly in patients with diabetic polyneropathy. OBJECTIVES: Explore the utility of VPT examination in CIDP patients. METHODS: CIDP subjects attending the Neuromuscular clinic between 01/2013 and 12/2014 were evaluated. Demographic data, clinical history, physical examination, VPT values, and electrophysiologic data from their charts were extracted. RESULTS: 70 charts were reviewed. 55 CIDP patients had elevated VPT, associated with higher frequency of abnormal sensory testing for various modalities (92.7% vs. 46.7%, p<0.0001), lower sensory and motor amplitudes and reduced conduction velocities on nerve conduction studies, and lower treatment response rates (54% vs. 93%, p = 0.01). CONCLUSION: VPT examination is a simple tool, which is a reliable and sensitive measure not only for diabetic neuropathy, but also for CIDP. Moreover, in CIDP, elevated VPT values are also associated with lower treatment response rates.

Treatment Responsiveness in CIDP Patients with Diabetes Is Associated with Higher Degrees of Demyelination.

INTRODUCTION: Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is one of several chronic treatable acquired demyelinating neuropathies. OBJECTIVES: To explore the association between the degree of demyelination in CIDP, and treatment responsiveness. METHODS: A retrospective chart review of CIDP subjects assessed between 1997 and 2013 was performed to compare treatment responsiveness using different sets of criteria. RESULTS: 99 CIDP patients were included, 34 with diabetes mellitus (DM). Treatment responsiveness was higher in CIDP-DM fulfilling 1 or more EFNS/PNS criteria, (63% vs. 31%, p = 0.03), and in CIDP+DM fulfilling 2 or more criteria (89% vs. 36%, p = 0.01). Nonetheless, treatment responsiveness in CIDP+DM had the highest odds ratio (3.73, p = 0.01). Similar results were also shown in simplified uniform study criteria, with 10% cut off values for CIDP-DM, compared to 30% for CIDP+DM. CONCLUSION: In CIDP+DM, higher degrees of demyelination are associated with treatment responsiveness, implying the need to adjust current criteria in these patients.

Choosing drugs for the treatment of diabetic neuropathy.

INTRODUCTION: Diabetic sensorimotor polyneuropathy (DSP) affects 50% of diabetes patients and is painful in about 26%. Although disease-modifying therapies are not available for DSP, symptomatic treatments for painful diabetic neuropathy (PDN) are effective. AREAS COVERED: We performed a MEDLINE search on PubMed using the search terms: treatment diabetic neuropathy and treatment PDN. This review outlines the problem posed by DSP, the clinical presentation and the characterization of PDN. A discussion of disease-modifying interventions, including the benefits of strict glycemic control, is followed by a focus on interventions for PDN including antidepressants, anticonvulsants and other treatments. EXPERT OPINION: Disease modification in DSP remains an unmet need in clinical medicine affecting a large percentage of the population with concomitant healthcare costs. Strict glycemic control and attention to potential risk factors such as hypertension, hyperlipidemia and obesity may minimize DSP. Many patients benefit from treatment of their painful symptoms with anticonvulsants or antidepressants, but all are associated with significant side effects that limit their usefulness. There is a need for treatments of PDN with fewer side effects and more effective pain relief.