Store-operated calcium entry dysfunction in CRAC channelopathy: Insights from a novel STIM1 mutation.

Store-operated calcium entry (SOCE) plays a crucial role in maintaining cellular calcium homeostasis. This mechanism involves proteins, such as stromal interaction molecule 1 (STIM1) and ORAI1. Mutations in the genes encoding these proteins, especially STIM1, can lead to various diseases, including CRAC channelopathies associated with severe combined immunodeficiency. Herein, we describe a novel homozygous mutation, NM_003156 c.792-3C > G, in STIM1 in a patient with a clinical profile of CRAC channelopathy, including immune system deficiencies and muscle weakness. Functional analyses revealed three distinct spliced forms in the patient cells: wild-type, exon 7 skipping, and intronic retention. Calcium influx analysis revealed impaired SOCE in the patient cells, indicating a loss of STIM1 function. We developed an antisense oligonucleotide treatment that improves STIM1 splicing and highlighted its potential as a therapeutic approach. Our findings provide insights into the complex effects of STIM1 mutations and shed light on the multifaceted clinical presentation of the patient.

Hereditary transthyretin amyloidosis in middle-aged and elderly patients with idiopathic polyneuropathy: a nationwide prospective study.

BACKGROUND: Hereditary transthyretin amyloidosis (ATTRv) is an adult-onset autosomal dominant disease resulting from TTR gene pathogenic variants. ATTRv often presents as a progressive polyneuropathy, and effective ATTRv treatments are available. METHODS: In this 5 year-long (2017-2021) nationwide prospective study, we systematically analysed the TTR gene in French patients with age >50 years with a progressive idiopathic polyneuropathy. RESULTS: 553 patients (70% males) with a mean age of 70 years were included. A TTR gene pathogenic variant was found in 15 patients (2.7%), including the Val30Met TTR variation in 10 cases. In comparison with patients with no TTR gene pathogenic variants (n = 538), patients with TTR pathogenic variants more often presented with orthostatic hypotension (53 vs. 21%, p = .007), significant weight loss (33 vs 11%, p = .024) and rapidly deteriorating nerve conduction studies (26 vs. 8%, p = .03). ATTRv diagnosis led to amyloid cardiomyopathy diagnosis in 11 cases, ATTRv specific treatment in all cases and identification of 15 additional ATTRv cases among relatives. CONCLUSION: In this nationwide prospective study, we found ATTRv in 2.7% of patients with age >50 years with a progressive polyneuropathy. These results are highly important for the early identification of patients in need of disease-modifying treatments.

Anti-disialosyl-immunoglobulin M chronic autoimmune neuropathies: a nationwide multicenter retrospective study.

BACKGROUND AND PURPOSE: In this retrospective study involving 14 university hospitals from France and Switzerland, the aim was to define the clinicopathological features of chronic neuropathies with anti-disialosyl ganglioside immunoglobulin M (IgM) antibodies (CNDA). RESULTS: Fifty-five patients with a polyneuropathy evolving for more than 2 months and with at least one anti-disialosyl ganglioside IgM antibody, that is, anti-GD1b, -GT1b, -GQ1b, -GT1a, -GD2 and -GD3, were identified. Seventy-eight percent of patients were male, mean age at disease onset was 55 years (30-76) and disease onset was progressive (82%) or acute (18%). Patients presented with limb sensory symptoms (94% of cases), sensory ataxia (85%), oculomotor weakness (36%), limb motor symptoms (31%) and bulbar muscle weakness (18%). Sixty-five percent of patients had a demyelinating polyradiculoneuropathy electrodiagnostic profile and 24% a sensory neuronopathy profile. Anti-GD1b antibodies were found in 78% of cases, whilst other anti-disialosyl antibodies were each observed in less than 51% of patients. Other features included nerve biopsy demyelination (100% of cases), increased cerebrospinal fluid protein content (75%), IgM paraprotein (50%) and malignant hemopathy (8%). Eighty-six percent of CNDA patients were intravenous immunoglobulins-responsive, and rituximab was successfully used as second-line treatment in 50% of cases. Fifteen percent of patients had mild symptoms and were not treated. CNDA course was progressive (55%) or relapsing (45%), and 93% of patients still walked after a mean disease duration of 11 years. CONCLUSION: Chronic neuropathies with anti-disialosyl ganglioside IgM antibodies have a recognizable phenotype, are mostly intravenous immunoglobulins-responsive and present with a good outcome in a majority of cases.

Phenotypical variability and atypical presentations in a French cohort of Andersen-Tawil syndrome.

BACKGROUND AND PURPOSE: Andersen-Tawil syndrome (ATS) is a skeletal muscle channelopathy caused by KCNJ2 mutations, characterized by a clinical triad of periodic paralysis, cardiac arrhythmias and dysmorphism. The muscle phenotype, particularly the atypical forms with prominent permanent weakness or predominantly painful symptoms, remains incompletely characterized. METHODS: A retrospective clinical, histological, electroneuromyography (ENMG) and genetic analysis of molecularly confirmed ATS patients, diagnosed and followed up at neuromuscular reference centers in France, was conducted. RESULTS: Thirty-five patients from 27 unrelated families carrying 17 different missense KCNJ2 mutations (four novel mutations) and a heterozygous KCNJ2 duplication are reported. The typical triad was observed in 42.9% of patients. Cardiac abnormalities were observed in 65.7%: 56.5% asymptomatic and 39.1% requiring antiarrhythmic drugs. 71.4% of patients exhibited dysmorphic features. Muscle symptoms were reported in 85.7%, amongst whom 13.3% had no cardiopathy and 33.3% no dysmorphic features. Periodic paralysis was present in 80% and was significantly more frequent in men. Common triggers were exercise, immobility and carbohydrate-rich diet. Ictal serum potassium concentrations were low in 53.6%. Of the 35 patients, 45.7% had permanent weakness affecting proximal muscles, which was mild and stable or slowly progressive over several decades. Four patients presented with exercise-induced pain and myalgia attacks. Diagnostic delay was 14.4 ± 9.5 years. ENMG long-exercise test performed in 25 patients (71.4%) showed in all a decremental response up to 40%. Muscle biopsy performed in 12 patients revealed tubular aggregates in six patients (associated in two of them with vacuolar lesions), dystrophic features in one patient and non-specific myopathic features in one patient; it was normal in four patients. DISCUSSION: Recognition of atypical features (exercise-induced pain or myalgia and permanent weakness) along with any of the elements of the triad should arouse suspicion. The ENMG long-exercise test has a high diagnostic yield and should be performed. Early diagnosis is of utmost importance to improve disease prognosis.

Atraumatic proximal radial nerve entrapment. Illustrative cases and systematic review of literature.

PURPOSE: The aims of the present study were to describe atraumatic proximal radial nerve entrapment (PRNE) and potential strategies for management. MATERIALS AND METHODS: We performed a comprehensive search of 4 electronic databases for studies pertaining to patients with atraumatic PRNE. Studies published between 1930 and 2020 were included. Clinical presentation, nerve conduction studies, electromyography, and treatment methods were reviewed. In order to outline management strategies, 2 illustrative cases of acute PRNE were presented. RESULTS: We analyzed 12 studies involving 21 patients with 22 PRNE (15 acute and 7 progressive). Sudden or repetitive elbow extension with forceful muscle contraction (n = 16) was the primary mechanism of injury. The two main sites of entrapment were the fibrous arch (n = 7) and hiatus of the lateral intermuscular septum (n = 7). Conservative treatment was performed in 4 patients and allowed for complete clinical recovery in all cases. The remaining 18 patients underwent epineurolysis (n = 16) or resection/repair of hourglass-like constriction (n = 2) between 1.5- and 120-months following diagnosis. Twelve patients experience complete recovery, while partial or no clinical recovery was reported in 1 and 4 cases, respectively; the outcome was unknown in 1 case. CONCLUSIONS: Atraumatic PRNE is rare and remains challenging with respect to diagnosis and treatment. Current literature suggests that primary sites of entrapment are the fibrous arch and hiatus of the radial nerve at the time of forceful elbow extension. LEVEL OF EVIDENCE: Case series (IV) & systematic review (I).

New Oral Anticoagulants vs. Vitamin K Antagonists Among Patients With Cardiac Amyloidosis: Prognostic Impact.

Background: Atrial arrhythmia (AA) is common among patients with cardiac amyloidosis (CA), who have an increased risk of intracardiac thrombus. The aim of this study was to explore the prognostic impact of vitamin K-antagonists (VKA) and direct oral anticoagulants (DOAC) in patients with CA. Methods and Results: 273 patients with CA and history of AA with long term anticoagulation-69 (25%) light chain amyloidosis (AL), 179 (66%) wild-type transthyretin amyloidosis (ATTRwt) and 25 (9%) variant transthyretin amyloidosis (ATTRv)-were retrospectively included between January 2012 and July 2020. 147 (54%) and 126 (46%) patients received VKA and DOAC, respectively. Patient receiving VKA were more likely to have AL with renal dysfunction, higher NT-proBNP and troponin levels. Patients with ATTRwt were more likely to receive DOAC therapy. There were more bleeding complications among patients with VKA (20 versus 10%; P = 0.013) but no difference for stroke events (4 vs. 2%; P = 0.223), as compared to patients with DOAC. A total of 124 (45%) patients met the primary endpoint of all-cause mortality: 96 (65%) and 28 (22%) among patients with VKAs and DOACs, respectively (P < 0.001). After multivariate analysis including age and renal function, VKA was no longer associated with all-cause mortality. Conclusion: Among patients with CA and history of AA receiving oral anticoagulant, DOACs appear to be at least as effective and safe as VKAs.

Hepatitis E Virus Quasispecies in Cerebrospinal Fluid with Neurological Manifestations.

Hepatitis E virus (HEV) infection can lead to a variety of neurological disorders. While HEV RNA is known to be present in the central nervous system, HEV quasispecies in serum and cerebrospinal fluid (CSF) have rarely been explored. We studied the virus' quasispecies in the blood and the CSF of five patients at the onset of their neurological symptoms. The samples of three patients suffering from meningitis, neuralgic amyotrophy and acute inflammatory polyradiculoneuropathy were taken at the acute phase of the HEV infection. The samples from the other two patients were taken during the chronic phase (5 years after HEV diagnosis) when they presented with clinical signs of encephalitis. We sequenced at least 20 randomly polyproline regions of the selected virus clones. Phylogenetic analysis of the virus variants in the blood and the CSF revealed no virus compartmentalization for the three acute-phase patients but there was clear evidence of HEV quasispecies compartmentalization in the CSF of the two patients during chronic infection. In conclusion, prolonged infection in the immunocompromised condition can lead to independent virus replication in the liver and the tissues, producing viruses in CSF.

Impact of Coronavirus Disease 2019 in a French Cohort of Myasthenia Gravis.

OBJECTIVE: To describe the clinical characteristics and outcomes of coronavirus disease 2019 (COVID-19) among patients with myasthenia gravis (MG) and identify factors associated with COVID-19 severity in patients with MG. METHODS: The CO-MY-COVID registry was a multicenter, retrospective, observational cohort study conducted in neuromuscular referral centers and general hospitals of the FILNEMUS (Filière Neuromusculaire) network (between March 1, 2020, and June 8, 2020), including patients with MG with a confirmed or highly suspected diagnosis of COVID-19. COVID-19 was diagnosed based on a PCR test from a nasopharyngeal swab or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) serology, thoracic CT scan, or typical symptoms. The main outcome was COVID-19 severity based on location of treatment/management (home, hospitalized in a medical unit, or in an intensive care unit). We collected information on demographic variables, general history, and risk factors for severe COVID-19. Multivariate ordinal regression models were used to identify factors associated with severe COVID-19 outcomes. RESULTS: Among 3,558 patients with MG registered in the French database for rare disorders, 34 (0.96%) had COVID-19. The mean age at COVID-19 onset was 55.0 ± 19.9 years (mean MG duration: 8.5 ± 8.5 years). By the end of the study period, 28 patients recovered from COVID-19, 1 remained affected, and 5 died. Only high Myasthenia Gravis Foundation of America (MGFA) class (≥IV) before COVID-19 was associated with severe COVID-19 (p = 0.004); factors that were not associated included sex, MG duration, and medium MGFA classes (≤IIIb). The type of MG treatment had no independent effect on COVID-19 severity. CONCLUSIONS: This registry-based cohort study shows that COVID-19 had a limited effect on most patients, and immunosuppressive medications and corticosteroids used for MG management are not risk factors for poorer outcomes. However, the risk of severe COVID-19 is elevated in patients with high MGFA classes (odds ratio, 102.6 [4.4-2,371.9]). These results are important for establishing evidence-based guidelines for the management of patients with MG during the COVID-19 pandemic.

Effect of familial clustering in the genetic screening of 235 French ALS families.

OBJECTIVES: To determine whether the familial clustering of amyotrophic lateral sclerosis (ALS) cases and the phenotype of the disease may help identify the pathogenic genes involved. METHODS: We conducted a targeted next-generation sequencing analysis on 235 French familial ALS (FALS), unrelated probands to identify mutations in 30 genes linked to the disease. The genealogy, that is, number of cases and generations with ALS, gender, age, site of onset and the duration of the disease were analysed. RESULTS: Regarding the number of generations, 49 pedigrees had only one affected generation, 152 had two affected generations and 34 had at least three affected generations. Among the 149 pedigrees (63.4%) for which a deleterious variant was found, an abnormal G4C2 expansion in C9orf72 was found in 98 cases as well as SOD1, TARBP or FUS mutations in 30, 9 and 7 cases, respectively. Considering pedigrees from the number of generations, abnormal G4C2 expansion in C9orf72 was more frequent in pedigrees with pairs of affected ALS cases, which represented 65.2% of our cohort. SOD1 mutation involved all types of pedigrees. No TARDBP nor FUS mutation was present in monogenerational pedigrees. TARDBP mutation predominated in bigenerational pedigrees with at least three cases and FUS mutation in multigenerational pedigrees with more than seven cases, on average, and with an age of onset younger than 45 years. CONCLUSION: Our results suggest that familial clustering, phenotypes and genotypes are interconnected in FALS, and thus it might be possible to target the genetic screening from the familial architecture and the phenotype of ALS cases.

Gateway and journey of patients with cardiac amyloidosis.

AIMS: Advances have been made over the last decade in the management of cardiac amyloidosis (CA), but a delayed diagnosis is still common. The aim of this study was to describe the journey to CA diagnosis from initial clinical and to analyse time to diagnosis. METHODS AND RESULTS: Between January 2001 and May 2019, 270 consecutive patients with CA diagnosed at Toulouse University Hospital were retrospectively included in this cross-sectional study: 111 (41%) light chain amyloidosis, 122 (45%) wild-type transthyretin amyloidosis, and 37 (14%) hereditary transthyretin amyloidosis. CA onset occurred mostly with dyspnoea (50%) or systematic follow-up (10%). The cardiologist was the first line specialist in 68% of patients, followed by the nephrologist (9%) and neurologist (8%). Patients encountered a median (minimum-maximum) number of two (1-7) physician specialists and performed a median (minimum-maximum) number of three (1-8) tests before diagnosis. Median delay between symptom onset and CA diagnosis was 8 [IQR 5-14], 10 [IQR 3-34], and 18 [IQR 4-49] months, respectively, in light chain amyloidosis, wild-type transthyretin amyloidosis, and hereditary transthyretin amyloidosis subgroups (P = .060). Having performed electromyography or spirometry was associated with a longer delay in diagnosis in the overall population: odds ratio = 1.13; 95% confidence interval 1.02 to 1.24; and odds ratio = 1.13; 1.03 to 1.24, respectively, probably due to non-specific initial symptoms. CONCLUSIONS: CA is a protean disease with various first line specialists causing a diagnostic wandering despite increasing medical community awareness. It requires a multidisciplinary specialist care networks to educate and manage symptoms and therapies.

Which Method for Diagnosing Small Fiber Neuropathy?

Introduction: Small fiber neuropathies (SFN) induce pain and/or autonomic symptoms. The diagnosis of SFN poses a challenge because the role of skin biopsy as a reference method and of each neurophysiological test remain to be discussed. This study compares six methods evaluating small sensory and autonomic nerve fibers: skin biopsy, Quantitative Sensory Testing (QST), quantitative sweat measurement system (Q-Sweat), Laser Evoked Potentials (LEP), Electrochemical Skin Conductance (ESC) measurement and Autonomic CardioVascular Tests (ACVT). Methods: This is a single center, retrospective study including patients tested for symptoms compatible with SFN between 2013 and 2016 using the afore-mentioned tests. Patients were ultimately classified according to the results and clinical features as "definite SFN," "possible SFN" or "no SFN." The sensitivity (Se) and specificity (Sp) of each test were calculated based on the final diagnosis and the best diagnostic strategy was then evaluated. Results: Two hundred and forty-five patients were enrolled (164 females (66.9%), age: 50.4 ± 15 years). The results are as follows: skin biopsy: Se = 58%, Sp = 91%; QST: Se = 72%, Sp = 39%; Q-Sweat: Se = 53%, Sp = 69%; LEP: Se = 66%, Sp = 89%; ESC: Se = 60%, Sp = 89%; Cardiovascular tests: Se = 15%, Sp = 99%. The combination of skin biopsy, LEP, QST and ESC has a Se of 90% and a Sp of 87%. Conclusion: Our study outlines the benefits of combining skin biopsy, ESC, LEP and QST in the diagnosis of SFN.

[Indication of autologous stem cell transplantation in chronic inflammatory demyelinating polyneuropathy: Guidelines from the Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC)]. / Indications de l'autogreffe de cellules souches hématopoïétiques dans la polyradiculonévrite inflammatoire démyélinisante chronique : recommandations de la Société francophone de greffe de moelle et de thérapie cellulaire (SFGM-TC).

Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) is a chronic autoimmune disease involving the peripheral nervous system, characterized by focal and segmental demyelination accounting for neurological deficit. CIDP diagnosis is based on several criteria and requires the presence of specific clinical symptoms and of demyelinating criteria on the electroneuromyogram (ENMG) or of additional supportive criteria (spinal fluid examination with dissociation between albumin level and cellular abnormalities, nervous abnormalities on MRI or other minor abnormalities on ENMG, demyelinating features on nerve biopsy or patient improvement under so-called first-line therapy with immunodulator treatment). After failure of two successive first line immunomodulating drug therapies (corticosteroids, immunomodulating immunoglobulins, or plasma exchange), several options can be considered as second line therapies. The efficacy of autologous hematopoietic cell transplantation (AHCT) has been shown in CIDP patients. The aim of these recommendations established by a working group of experts from the "Société française de greffe de moelle osseuse et thérapie cellulaire (SFGM-TC)", the group "maladies auto-immunes et thérapie cellulaire (MATHEC)" and the "filière de santé maladies rares neuromusculaire (FILNEMUS)" is to specify the eligibility criteria for AHCT in CIPD patients, to describe the mobilization and the conditioning regimen for the AHCT procedure, as well as the patient standardized post-transplant follow-up and the management of neurological treatment throughout the all procedure.

Atrial fibrillation and subtype of atrial fibrillation in cardiac amyloidosis: clinical and echocardiographic features, impact on mortality.

Background: Atrial fibrillation (AF) commonly affects patients with cardiac amyloidosis (CA). Amyloid deposition within the left atrium may be responsible for the subtype of AF in either permanent or non-permanent form. The prognostic implications of AF and its clinical subtype according to the type of CA are still controversial in this population. This study sought to investigate the prevalence, incidence and prognostic implications of AF and the clinical subtype of AF (permanent or non-permanent) in patients with CA. Methods: Two hundred and thirty-eight patients with CA and full medical records were retrospectively enrolled in the study: About 115 (48%) with light chain (AL) amyloidosis and 123 (52%) with transthyretin amyloidosis (ATTR). Patient's medical records were reviewed to establish baseline prevalence, incidence and impact on all-cause and cardiovascular mortality during follow-up of AF. Results: One hundred and four (44%) patients had history of AF at the time of diagnosis: 62 (60%) permanent and 42 (40%) non-permanent. There were 30 (26%) and 74 (60%) patients with history of AF among patients with AL and ATTR (including 5 hereditary and 69 wild-type), respectively (p<.0001). During the follow-up, 48 new patients developed AF (29, 12 and 7 among patients with AL, wild-type ATTR and hereditary ATTR). After adjustment for age, survival was similar in patients with or without history of AF (HR 0.87 (95% CI, 0.60 to 1.27; p = .467). AF had no impact on cardiovascular mortality. Among the 152 patients with history of AF included in the whole study, there were 75 (49%) patients with permanent AF. After adjustment for age, survival was similar in patients with permanent and non-permanent AF: HR 1.29 (95% CI, 0.84 to 1.99; p = .251). The results were the same among patients with AL or wild-type amyloidosis. Subtype of AF had no impact on cardiovascular mortality. Conclusions: AF is common in patients with CA. However, AF and clinical subtype of AF have no impact on all-cause mortality, whatever the type of amyloidosis.

Unusual association of amyotrophic lateral sclerosis and myasthenia gravis: A dysregulation of the adaptive immune system?

Myasthenia gravis is an autoimmune disorder affecting neuromuscular junctions that has been associated with a small increased risk of amyotrophic lateral sclerosis (ALS). Here, we describe a retrospective series of seven cases with a concomitant diagnosis of ALS and myasthenia gravis, collected among the 18 French reference centers for ALS in a twelve year period. After careful review, only six patients strictly met the diagnostic criteria for both ALS and myasthenia gravis. In these patients, limb onset of ALS was reported in five (83%) cases. Localization of myasthenia gravis initial symptoms was ocular in three (50%) cases, generalized in two (33%) and bulbar in one (17%). Median delay between onset of the two conditions was 19 months (6-319 months). Anti-acetylcholine receptor antibodies testing was positive in all cases. All patients were treated with riluzole and one had an associated immune-mediated disease. In the one last ALS case, the final diagnosis was false-positivity for anti-acetylcholine receptor antibodies. The co-occurrence of ALS and myasthenia gravis is rare and requires strict diagnostic criteria. Its demonstration needs thoughtful interpretation of electrophysiological results and exclusion of false positivity for myasthenia gravis antibody testing in some ALS cases. This association may be triggered by a dysfunction of adaptive immunity.

Prevalence of type 1 Brugada ECG pattern after administration of Class 1C drugs in patients with type 1 myotonic dystrophy: Myotonic dystrophy as a part of the Brugada syndrome.

BACKGROUND: Both type 1 myotonic dystrophy (MD1) and Brugada syndrome (BrS) may be complicated by conduction disturbances and sudden death. Spontaneous BrS has been observed in MD1 patients, but the prevalence of drug-induced BrS in MD1 is unknown. OBJECTIVE: The purpose of this study was to prospectively assess the prevalence of type 1 ST elevation as elicited during pharmacologic challenge with Class 1C drugs in a subgroup of MD1 patients and to further establish correlations with ECG and electrophysiologic variables and prognosis. METHODS: From a group of unselected 270 MD1 patients, ajmaline or flecainide drug challenge was performed in a subgroup of 44 patients (27 men, median age 43 years) with minor depolarization/repolarization abnormalities suggestive of possible BrS. The presence of type 1 ST elevation after drug challenge was correlated to clinical, ECG, and electrophysiologic variables. RESULTS: Eight of 44 patients (18%) presented with BrS after drug challenge. BrS was seen more often in men (26% vs 6%, P = .09) and was related to younger age (35 vs 48 years, P = .07). BrS was not correlated to symptoms, baseline ECG, HV interval, results of signal-averaged ECG, or abnormalities on ambulatory recordings. MD1 patients with BrS had longer corrected QT intervals, greater increase in PR interval after drug challenge, and higher rate of inducible ventricular arrhythmias (62% vs 21%, P = .03). Twelve patients were implanted with a pacemaker and 5 with an implantable cardioverter-defibrillator. Significant bradycardia did not occur in any patients, and malignant ventricular arrhythmia never occurred during median 7-year follow-up (except 1 hypokalemia-related ventricular fibrillation). CONCLUSION: BrS is elicited by a Class 1 drug in 18% of MD1 patients presenting with minor depolarization/repolarization abnormalities at baseline, but the finding seems to be devoid of a prognostic role.

Bent spine syndrome (camptocormia): a retrospective study of 63 patients.

OBJECTIVES: Bent spine syndrome (BSS) is characterized by involuntary forward flexion of the trunk in the standing position but not in the recumbent position. We assessed the causes of BSS based on findings in 63 patients. METHODS: We retrospectively reviewed the records of all patients with BSS evaluated at a teaching hospital in Toulouse, France, between 1995 and 2006. For each patient, we recorded the findings from the following investigations: physical examination, electromyogram (EMG), creatine phosphokinase (CPK) assay, computed tomography (CT), and surgical muscle biopsy. RESULTS: We identified 63 patients, 46 females and 17 males, with a mean age of 70 ± 6.9 years. Among them, 40 had delayed-onset paraspinal myopathy, with fatty infiltration predominantly affecting the paraspinal muscles. In 40% of these patients, CT disclosed mild fatty infiltration of the gluteal and posterior thigh and leg muscles in addition to the paraspinal muscle abnormalities. Paraspinal muscle histology showed lobular endomysial fibrosis, as previously described and ruled out other forms of muscle dystrophy. The remaining 23 patients (14 females and nine males) had either another neurological disease or myopathic involvement of other muscles, with a definite diagnosis; nevertheless, forward bending of the trunk was the most prominent symptom and the reason for the initial physician visit. CONCLUSION: In our case-series, delayed-onset paraspinal myopathy accounted for 64% of cases of BSS. The most informative investigation was CT, which showed a patchy decrease in paraspinal muscle density.