A Case Report and Literature Review of Charcot-Marie-Tooth Disease Type 2F in a Family

On the basis of strong research evidence, Duchenne muscular dystrophy (DMD), the most common severe childhood form of muscular dystrophy, is an X-linked recessive disorder caused by out-of-frame mutations of the dystrophin gene. Thus, it is classified asa dystrophinopathy. The disease onset is before age 5 years. Patients with DMD present with progressive symmetrical limb-girdle muscle weakness and become wheelchair dependent after age 12 years. (2)(3). On the basis of some research evidence,cardiomyopathy and congestive heart failure are usually seen in the late teens in patients with DMD. Progressive scoliosis and respiratory in sufficiency often develop once wheelchair dependency occurs. Respiratory failure and cardiomyopathy are common causes of death, and few survive beyond the third decade of life. (2)(3)(4)(5)(6)(7). On the basis of some research evidence, prednisone at 0.75 mg/kg daily (maximum dose, 40 mg/d) or deflazacort at 0.9 mg/kg daily (maximum dose, 39 mg/d), a derivative of prednisolone (not available in the United States), as a single morning dose is recommended for DMD patients older than 5 years, which may prolong independent walking from a few months to 2 years. (2)(3)(16)(17). Based on some research evidence, treatment with angiotensin-converting enzyme inhibitors, b-blockers, and diuretics has been reported to be beneficial in DMD patients with cardiac abnormalities. (2)(3)(5)(18). Based on expert opinion, children with muscle weakness and increased serum creatine kinase levels may be associated with either genetic or acquired muscle disorders (Tables 1 and 3). (14)(15)

The incidence of elevated serum creatine kinase (CK) and pyruvate kinase (PK) activities was compared in 20 definite carriers of Duchenne muscular dystrophy (DMD), 47 possible carriers, and 42 female controls. When adult age was not regarded as a variable, 70% of the definite carriers had elevated PK, 55% had elevated CK, and 75% had elevated PK or elevated CK or both, 38% of the possible carriers had elevated PK, 19% had elevated CK, and 40% had elevated PK or elevated CK or both. The detection efficiency of the CK test was influenced by the age of the subjects: the upper normal limit of serum CK in the adult controls was at the minimum between 21 and 35 years of age, and CK activity in some carriers declined from elevated to normal levels with increasing age. With these considerations, 70% of definite carriers had elevated CK and 80% had elevated PK and/or CK; 34% of the possible carriers had elevated CK and 43% had elevated PK and/or CK. On the basis of the PK and CK measurements, only 16 of 24 possible carrier mothers were likely to be DMD carriers, implying that the other 8 were non-carrier mothers of new mutant sons.

BackgroundIt is not well defined whether Guillain–Barré syndrome (GBS) patients with elevated serum creatine kinase (CK) levels have characteristic clinical features and are related to the subgroups of GBS.MethodsWe retrospectively studied 51 consecutive patients with GBS, who visited our hospital, and compared clinical, laboratory and electrophysiological findings between patients with and without elevated CK levels.ResultsOf 51 patients, 14 patients (27%) showed an elevation of serum CK levels. When compared with patients with the normal CK levels, the ratios of male, antecedent infections, and anti-GM1 antibody positivity were significantly higher in patients with elevated CK levels. The ratios of hypoesthesia, cranial nerve involvement, and urinary retention were significantly less in patients with elevated CK levels. There were no significant differences in disability at peak between two groups. In the electrophysiological examination, sensory nerve abnormalities were not observed. Although some patients with elevated CK levels showed prolongation of distal motor latencies (DMLs) and increase of durations in the initial examination, development of the prolongation of DMLs and increase of durations was not observed in the follow-up examinations. The findings were consistent with acute motor axonal neuropathy (AMAN) with reversible conduction failure (RCF) but not acute inflammatory demyelinating polyneuropathy (AIDP).ConclusionsThe results suggest that the GBS patients with elevated CK levels represent not a group of AIDP but a group of AMAN with axonal degeneration or RCF even though the initial electrophysiological examination shows AIDP pattern.

<h3>Objective:</h3> NA <h3>Background:</h3> NA <h3>Design/Methods:</h3> We present a patient with persistently elevated creatinine kinase and a clinical syndrome consistent with adult-onset spinal muscular atrophy (dSMA) without pontocerebellar atrophy secondary to a vaccinia-related kinase 1 (VRK1) mutation. <h3>Results:</h3> A 46-year-old male presented for evaluation of persistently elevated creatinine kinase, leg weakness, and decreased balance for more than 5 years. He reported mild weakness mainly in the lower extremities and reduced calf size. The patient has had persistently elevated creatine kinase (CK) for the past 5 years, ranging from 580–7,000 units/L. On examination, he had bilateral high arches, calf fasciculations, and atrophy. Motor showed decreased strength in feet dorsiflexion and minimal bilateral hand interosseous weakness. Reflexes were normal except for the absent left ankle reflex. The rest of the neurologic examination was unremarkable. EMG/NCS showed reduced motor responses with diffuse neurogenic changes in the right arm and leg concerning for motor neuropathy. CK level remained elevated along with aldolase; otherwise negative myopathy labs. The neuropathy panel showed two pathogenic mutations of the VRK1 gene, variant c1072C&gt;T (p.Arg358) and c.356 A&gt;G (p.His119Arg), consistent with compound heterozygosity. <h3>Conclusions:</h3> VRK1 mutation is a rare cause of distal predominant spinal muscular atrophy. This disease is characterized by slowly progressive distal symmetric limb muscle weakness and atrophy, frequently leading to foot deformities such as pes cavus, with minimal or no sensory involvement. Mild elevations in CK can be seen in up to 50% of motor neuron disease cases. Our patient’s presentation was consistent with adult-onset spinal muscular atrophy. There was no pontocerebellar hypoplasia, which has also been described with this mutation. Creatine kinase level remained very elevated in our patient, beyond what has previously been described in the literature. Future investigation should be done to determine the significance of this, including whether there may be a myopathic component to this illness. <b>Disclosure:</b> Dr. Rodriguez-Hernandez has nothing to disclose. Dr. Carranza-Renteria has nothing to disclose. Dr. Faktorovich has a non-compensated relationship as a Board of Directors with Brother’s Brother Foundation that is relevant to AAN interests or activities.

Objective: We aimed to investigate the effect of serum Creatine Kinase (CK) levels on disease progression and prognosis in coronavirus disease 2019 (COVID-19). Methods: This was a retrospective study of 1751 COVID-19 patients at Leishenshan hospital in Wuhan, China. All patients were grouped to normal and elevated CK groups. Univariate and multivariate Cox regression analyses were performed to explore the relationship between mortality and CK levels. Univariate and multivariate logistic regression analyses were performed to explore the relationship between disease severity and CK levels. Survival curves were generated for normal and elevated CK groups. Fitting curves were performed to investigate the relationships between the number of days in hospital and Computed Tomography (CT) score. Results: Elevated CK patients had higher incidences of critical disease severity (P<0.001), death, and higher CT score. There was an association between elevated CK levels and mortality on multivariate Cox regression analysis (HR=7.31; 95% CI, 1.09-48.96; P=0.04). Elevated CK patients were more likely to have critical disease severity on multivariate logistic regression analysis (OR=4.38; 95% CI, 1.16-16.49; P=0.029). Kaplan-Meier curves demonstrated poor prognosis with elevated CK levels (P<0.001). Conclusion: Elevated CK level was an independent risk factor of mortality in COVID-19 patients. Inpatients with elevated CK had a higher risk for mortality, as well as critical severity condition compared with normal CK inpatients. This may help clinicians make more targeted drug choices to treat COVID-19 patients.

Serum creatine kinase (CK) elevation can occur in some patients with Graves' disease treated with antithyroid drugs (ATDs). This study retrospectively investigated clinical characteristics and biochemical data of patients with Graves' disease who experienced serum CK elevation during ATD treatment. CK elevation was observed in 29.6% (37/125) of patients, with 11.2% (14/125) being symptomatic. This incidence is higher than previously reported (13.5%). There were no differences in pre-treatment characteristics between patients with and without CK elevation. The intervals between the initiation of ATD treatment or normalization of thyroid function and the onset of CK elevation were 11.3±8.0 and 5.8±6.6 weeks, respectively, and peak serum CK levels averaged 441.9±394.0 IU/l. Markedly elevated serum CK were accompanied by increased serum myoglobin levels. Serum CK elevation occurred either continuously or intermittently, or as a single episode during the course of treatment. Thyroid function at the time of CK elevation varied from hyperthyroid to normal to hypothyroid. In conclusion, serum CK elevation in patients with Graves' disease treated with ATDs is not uncommon, with symptomatic cases accounting for approximately 10%, and the frequency increasing to around 30% when asymptomatic cases are included. The characteristics observed in our patients suggest the involvement of alternative, as yet unknown mechanisms beyond the relative hypothyroidism theory and the ATD side-effect theory in the development of CK elevation during ATD treatment in patients with Graves' disease.

Increased Serum Total Creatine Kinase and Creatine Kinase Isoenzyme MB After Cryosurgical Ablation of the Prostate

Extensive clinical investigation throughout the 1990s validated periprocedural myonecrosis as a powerful predictor of adverse outcomes, so it is surprising that this remains a contentious point. Originally derided as “enzyme leaks” or “myocardial infarctlets,” periprocedural myocardial infarction (MI) has now been definitively linked in large data sets to long-term adverse outcomes, most notably mortality. It is not, however, always directly contributory or causative. For example, a large creatine kinase (CK) elevation caused by closure of a major side branch resulting in chest pain and development of new Q waves is obviously undesirable and causally related to the interventional procedure. Alternatively, even small, asymptomatic CK elevations have been clearly associated with worse long-term outcome, and although this may in part be causally related to the procedure, it is more likely that the relationship is caused by the underlying predisposing factors that led to the periprocedural MI, such as arterial inflammation predilecting to the occurrence of embolization or to a large degree of atheroma burden leading to more myonecrosis. Under these circumstances, it is likely that the heightened inflammatory state and the diffuse disease that is present are the real causative factors for worse long-term outcomes. Recently, aspirin resistance has been demonstrated to predict periprocedural myonecrosis. Thus, both through direct causation and also as an epiphenomenon, embolization and attendant periprocedural myonecrosis are associated with short, intermediate, and long-term adverse outcomes (Table 1). This review details this evolution in thought. View this table: TABLE 1. Mechanisms Behind Periprocedural Myonecrosis Periprocedural myonecrosis is a frequent occurrence in percutaneous coronary intervention (PCI). CK or CK myocardial band (CK-MB) elevation occurs in ≈25% of patients undergoing PCI. With the advent of sensitive troponin measurements, it is clear that at least 50% of patients undergoing PCI have postprocedural troponin elevation, reflecting the frequency with which embolization occurs. However, troponin offers …

Rhabdomyolysis due to trauma and burns is an important cause of acute renal failure (ARF) secondary to myoglobinuria. To prevent morbidity and mortality from ARF due to rhabdomyolysis, early detection of ARF by monitoring the biochemical parameters such as serum creatinine, serum creatine kinase (CK), and urinary myoglobin (UM) can be helpful. The aims of the study were (1) to detect ARF due to rhabdomyolysis using serum creatinine, serum CK, and UM in trauma and electrical burn patients (2) to compare utility of these parameters in early prediction of ARF in patients of rhabdomyolysis. A total of 50 patients with trauma and electrical burns were included in the study. Serum creatinine, serum CK, and UM measurements were done at the time of admission and after 48h. Diagnosis of ARF was made in the patients by Rifle's criteria. The presence of significant elevation of creatinine, serum CK, and UM at the time of admission and after 48h was compared in patients developing ARF by Fisher's exact test. Fifteen of the 50 patients developed ARF as per the defined criteria. Of these, 9 patients (60 %) had raised level of serum creatinine above 1.4mg% at admission and 14 patients (93.33 %) had CK level >1250U/L at admission, whereas UM was positive in 6 (40 %) patients. Serum creatinine was significantly raised in all of the 15 ARF patients (100 %) after 48h of admission and serum CK was raised in 14 of the 15 ARF patients (93.33 %). UM was negative in all the patients after 48h of admission. Statistical analysis showed that rise in serum CK on admission was significantly increased in patients developing ARF as compared with serum creatinine and UM (P < 0.0001). On admission, CK is a better predictor of ARF due to rhabdomyolysis than creatinine and UM. Initial creatinine is a better predictor of ARF due to rhabdomyolysis than UM. UM assay is not a good investigation for early prediction of ARF in rhabdomyolysis.

Implications of increased myocardial isoenzyme level in the presence of normal serum creatine kinase activity

BackgroundThere has been no prior inception cohort data regarding incidence of cardiopulmonary complications and survival in early SSc patients comparing between those with elevated creatine kinase (baseline CK ≥ 500...

Serum creatine kinase (CK) levels are commonly used to judge the severity of muscle damage and to determine when to hospitalize patients who present with symptoms of exertional rhabdomyolysis in order to prevent renal failure. However, no CK standard exists because of the limited information available regarding exercise-induced CK elevation and renal function. This study determined the magnitude of CK elevation and the effect on renal function produced by exercise in a large subject group. Blood samples were obtained from 203 volunteers who performed 50 maximal eccentric contractions of the elbow flexor muscles. The samples, taken before and 4, 7, and 10 d after exercise, were analyzed for markers of muscle damage (CK, myoglobin (Mb), lactate dehydrogenase, alanine aminotransferase, and aspartate aminotransferase and for measures of renal function (creatinine, blood urea nitrogen, phosphorus, potassium, osmolality, and uric acid). All indicators of muscle damage increased significantly after exercise (P < 0.01). CK levels were 6420, 2100, and 311% above baseline on days 4, 7, and 10 after the exercise, respectively (P < 0.01), and Mb was 1137, 170, and 28% above baseline on days 4, 7, and 10 after exercise, respectively (P < 0.01). Of the 203 participants, 111 had CK values at 4 d postexercise > 2,000 U x L(-1) and 51 had values > 10,000 U x L(-1), levels used to diagnose myopathy (e.g., statin myositis) and rhabdomyolysis, respectively. There were no significant increases in any measure of renal function. Despite marked CK and Mb elevations in some subjects, none experienced visible myoglobinuria or required treatment for impaired renal function. Exertional muscle damage produced by eccentric exercise in healthy individuals can cause profound CK and Mb elevations without renal impairment.

Cabozantinib is a multikinase inhibitor approved for the treatment of metastatic medullary thyroid cancer and advanced renal cell carcinoma (RCC) in patients who have received prior anti-angiogenic therapy. While associations between serum creatine kinase (CK) elevations and other tyrosine kinase inhibitors used for the treatment of solid malignancies have been previously reported, we report a case of cabozantinib-associated CK elevation that was associated with musculoskeletal complaints by an RCC patient. Nine days following initiation of cabozantinib, the patient reported muscle cramps and serum CK had increased from levels 12months earlier that were within normal limits to a grade 1 elevation of 244units/L. Despite a dose reduction, her CK continued to rise over the next 2months, leading to a peak CK of 914units/L. Due to this grade 3 elevation, cabozantinib was permanently discontinued, and her CK subsequently returned to a grade 1 elevation within one week and then to baseline within 3weeks. The temporal relationship between drug exposure and CK increase strongly suggests causality. To the authors' knowledge, this is the first reported case of CK elevation attributed to cabozantinib, but cabozantinib-induced CK elevations could be under-reported, and providers should monitor for musculoskeletal complaints during cabozantinib therapy.

Motor neuron disorders (MNDs) are a heterogeneous group of diseases that result from degeneration of motor neurons. If both upper and lower motor neurons (UMNs and LMNs) are affected, the...

BackgroundMany patients after stroke are found to have elevated serum creatine kinase (CK). This study aimed to investigate the associations between serum CK levels and clinical outcomes in patients with acute ischemic stroke or transient ischemic attack.Methods and ResultsThe study included 8910 patients with acute ischemic stroke or transient ischemic attack from the CNSR‐III (Third China National Stroke Registry). Baseline serum CK levels after admission were measured. The associations between CK and clinical outcomes (stroke recurrence, death, and disability, defined as modified Rankin scale score 3–6 or 2–6) were analyzed. Patients with elevated CK levels had higher risks of recurrent stroke (hazard ratio [HR], 1.53; 95% CI, 1.21–1.93), death (HR, 1.68; 95% CI, 1.10–2.58), and disability (modified Rankin scale score, 3–6; odds ratio, 1.57; 95% CI, 1.29–1.90) at 3 months after adjusting confounding factors. Similar results were found at 1 year. The effects of CK on death and disability were more significant in male patients than female patients (P value for interaction <0.05). Elevated CK‐MB levels were not associated with clinical outcomes in this study.ConclusionsElevated serum CK after ischemic stroke or transient ischemic attack is associated with higher risks of recurrent stroke, death, and disability at 3 months and 1 year. Serum CK may act as a useful predictor for recurrent stroke and poor functional outcomes in patients with acute ischemic stroke or transient ischemic attack. Sex modifies the relationship between elevated CK and disability or death.